Hemostatic Profile Research Articles

Thromboelastometry: studying hemostatic profile in small for gestational age neonates-a pilot observational study.

Scarce data exists about the hemostatic status of small for gestational age (SGA) neonates. We aimed at evaluating the hemostatic profile of SGA neonates, using thromboelastometry (TEM). This is an observational study performed in a Greek tertiary General Hospital during an 18-month period. Ninety-three neonates were included in the study: 48 appropriate for gestational age weight (AGA) neonates and 45 SGA neonates Extrinsically activated TEM (ex-TEM) parameters, such as clotting time, clot formation time, amplitude recorded at 5 and 10min, a angle, maximum clot firmness, lysis index at 60min, and also platelet count, were used for the evaluation of the hemostatic profile in all neonates. No statistically significant differences were noticed regarding all ex-TEM parameters between AGA and SGA neonates, while no event of hemorrhage or thrombosis was noticed in the study population.Conclusions: The coagulation system of SGA neonates seems to be fully functional, with no evident tendency toward coagulopathy or thrombosis, when compared with AGA neonates. TEM seems to provide a promising and valid assessment of coagulation and fibrinolysis systems and may be used as a valuable biomarker, in the future. Further studies, with large samples, are necessary to confirm our results. What is Known: • SGA neonates may present coagulation disorders mainly due to hepatic dysfunction, polycythemia, and thrombocytopenia owing to long-term intrauterine hypoxia. • In the literature, despite the statistically significant differences in laboratory results between SGA and AGA neonates, no clinical manifestations of significantly altered hemostasis were recorded. Data of TEM interpretation of hemostasis in SGA neonates are not available. What is New: • TEM seems to interpret coagulation mechanism of preterm and full-term SGA neonates and confirm previous relevant literature findings regarding hemostasis in these neonates.

Trauma Resuscitation Consideration: Sex Matters

Sex dimorphisms in coagulation have been recognized, but whole blood assessment of these dimorphisms and their relationship to outcomes in trauma have not been investigated. This study characterizes the viscoelastic hemostatic profile of severely injured patients by sex, and examines how sex-specific coagulation differences affect clinical outcomes, specifically, massive transfusion (MT) and death. We hypothesized that severely injured females are more hypercoagulable and therefore, have lower rates of MT and mortality. Hemostatic profiles and clinical outcomes from all trauma activation patients from 2 level I trauma centers were examined, with sex as an experimental variable. As part of a prospective study, whole blood was collected and thrombelastography (TEG) was performed. Coagulation profiles were compared between sexes, and association with MT and mortality were examined. Poisson regression with robust standard errors was performed. Overall, 464 patients (23% female) were included. By TEG, females had a more hypercoagulable profile, with a higher angle (clot propagation) and maximum amplitude (MA, clot strength). Females were less likely to present with hyperfibrinolysis or prolonged activating clotting time than males. In the setting of depressed clot strength (abnormal MA), female sex conferred a survival benefit, and hyperfibrinolysis was associated with higher case-fatality rate in males. Severely injured females have a more hypercoagulable profile than males. This hypercoagulable status conferred a protective effect against mortality in the setting of diminished clot strength. The mechanism behind these dimorphisms needs to be elucidated and may have treatment implications for sex-specific trauma resuscitation.

Haemostatic Profiles are Similar across All Aetiologies of Cirrhosis

Patients with cirrhosis may acquire profound changes in haemostasis. Although haemostatic changes in cirrhosis have been extensively studied, most studies were performed in groups of patients with mixed aetiology. As thrombotic events appear more common in some aetiologies of disease, notably non-alcoholic steatohepatitis (NASH) and cholestatic disease, we hypothesized that haemostatic changes might be different across aetiologies. We studied 109 patients with cirrhosis (31 cholestatic liver disease, 23 NASH, 37 alcoholic liver disease [ALD], 18 viral hepatitis) and 44 healthy controls. Patients with malignancy were excluded. Routine diagnostic tests of haemostasis, thrombin generation assays, fibrin permeability assays and a plasma-based fibrinolytic assay were performed. All patients had comparable severity of disease according to their Model for End-Stage Liver Disease score (9 [7-11]). Plasma levels of von Willebrand factor were substantially elevated across all aetiologies, with a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 levels comparable to controls. Thrombin generation capacity was elevated in all aetiologies, most profoundly in ALD. Fibrin permeability was decreased in all aetiologies, which was accompanied by elevated fibrinogen levels. Clot lysis times were prolonged in NASH and cholestatic disease. Plasma levels of individual proteins were similarly altered in all aetiologies. Our in-depth haemostatic profiling of primary, secondary and tertiary haemostasis in a group of patients with Childs-Turcotte-Pugh A/B cirrhosis showed no large differences between aetiologies, and was consistent with a general hypercoagulable profile in patients with mild cirrhosis. These results suggest that patients with cirrhosis have an increased risk of thrombosis, irrespective of their aetiology.

Influence of Amlodipine on Haemostatic Measurements during Clopidogrel Treatment in Patients with Coronary Artery Disease.

Amlodipine has a potential to reduce clopidogrel bioactivation through the cytochrome P450 3A4 enzyme in vivo, but the clinical impact of this interaction remains controversial. This randomized, open-label, two-period, crossover study was performed to evaluate the influence of amlodipine on the haemostatic profiles of high-risk patients during clopidogrel treatment. We recruited 40 Asian patients (Male/Female: n = 36/4) receiving clopidogrel (75 mg/day), aspirin (100 mg/day) and rosuvastatin for at least 6 months following percutaneous coronary intervention. Patients were randomly assigned to receive either 5 mg daily amlodipine or not for 2 weeks, and then were crossed over to the other treatment for 2 weeks. Haemostatic measurements were conducted with the VerifyNow assay and thromboelastography (TEG). Primary endpoint was P2Y12 Reaction Units (PRU) during on- versus off-amlodipine treatment. The on-amlodipine strategy showed higher level of PRU compared with the off-amlodipine strategy (176.8 ± 75.4 vs. 150.7 ± 65.5 PRU; ∆mean: 26.1 PRU; ∆95% confidence interval [CI]: 4.5-47.7 PRU; p = 0.019). Platelet-fibrin clot strength measured by TEG was lower during on- versus off-amlodipine treatment (7,712 ± 1,889 vs. 8,559 ± 2,174 dyne/cm2; ∆mean: -847 dyne/cm2; ∆95% CI: -1,632 to -62 dyne/cm2; p = 0.035). After amlodipine discontinuation, 27 patients (67.5%) showed a decrease in PRU, which was associated with 'PRU ≥ 160 on-amlodipine' in multivariate analysis (odds ratio: 62.014; 95% CI: 2.302-1670.328; p = 0.014). In conclusion, amlodipine increases platelet reactivity and decreases platelet-fibrin clot strength during clopidogrel treatment. In addition, the effect of amlodipine discontinuation on clopidogrel responsiveness is associated with on-amlodipine platelet reactivity.

Effect of perinatal risk factors on coagulation system in premature infants

Background: neonates have different blood clotting and fibrinolytic activities from the adults. Compared with full-term infants, premature infants are more prone to bleeding diathesis after birth, such as intracranial hemorrhage and pulmonary hemorrhage. The defective coagulation factors in premature infants contribute to predisposition of bleeding in premature infants. Objective: it wasto assess the hemostatic profile by screening tests in preterm infants with perinatal risk factors. Patients and Methods: the study was conducted on 90 subjects, 30 preterm with risk factors, 20 preterm without risk factors, 30 full term and 10 adults. All of them were subjected to full clinical history, examination and routine investigation including CBC, prothrombin time, activated partial thromboplastin time, thrombin time and fibrinogen concentration. Results: the results of this study revealed a prolongation in the PT, APTT and TT together with a lower fibrinogen concentration in the group of preterm without risk factors in comparison with the group of full term and adult and revealed that there is more prolongation in the PT, APTT and TT together with more decrease in fibrinogen concentration in the group of preterm with risk factors in comparison with the group of preterm without risk factors, full term and adult but there is no significant difference between full term and adult as regard PT, APTT, TT and fibrinogen concentration. Conclusion: preterm infants without perinatal risk factors show a lower hemostatic profile when compared with healthy full term and adult. Preterm infants with perinatal risk factors show more decrease in hemostatic profile when compared with healthy full term and adult. Perinatal risk factors (preeclampsia, diabetes and urinary tract infection) seem to interfere with coagulation protein synthesis.

Quantitative morphological characteristics of platelet hemostasis in patients with type 1 and 2 diabetes mellitus depending on the glomerular filtration rate.

Background. The use of only a complex of clinical and laboratory parameters characterizing the state of the kidneys and a lipid profile profile with anamnestic data to determine the initial manifestations of functional renal insufficiency is not sufficient. This necessitates the search for new, more informative markers for the risk of development and progression of diabetic nephropathy in type 1 diabetes mellitus patients, which may be endothelial dysfunction markers and morphological parameters of thrombocyte hemostasis. Objective. The purpose of the study is to analyze the quantitative parameters of platelet hemostasis in patients with diabetes mellitus type 1 and type 2, depending on the velocity of glomerular filtration rate. Methods. Transmission electron microscopy and phase contrast microscopy quantitatively assessed the state of platelet hemostasis in the blood of 66 patients with type 1 diabetes mellitus and 58 patients with type 2 diabetes mellitus, depending on the velocity of glomerular filtration rate. Results. Quantitative characterization of the morphological features of platelet hemostasis revealed early signs of damage to the platelet structure, which occur at normal levels of glomerular filtration rate in patients with diabetes mellitus type 1 and type 2. Increased degranulation of alpha-granules and the growth of circulating platelet aggregates in the setting of significant activation of thrombocytes in the hyaline type are the most sensitive signs of hemostasis disorder in patients without clinical signs of diabetic kidney disease. The degree of pathomorphological changes in platelet count in patients with type 2 diabetes mellitus is higher than that of type 1 diabetes mellitus. With the progression of diabetic nephropathy, there is a significant deepening of platelet hemostasis disorders with the involvement of ultrastructural lesions of erythrocytes and leukocytes, massive platelet degranulation, the formation of numerous complex platelets, consolidation of correlations between the greater part of morphological parameters characterizing the hemostatic profile in patients with diabetes mellitus 1 and 2 type. Conclusion. Morphological changes in platelet hemostasis in patients with diabetes mellitus occur to the clinical manifestations of diabetic kidney disease and clearly correlate with the profundity of diabetic nephropathy at the stages of its development.

Elevated Plasma Levels of Cell-Free DNA During Liver Transplantation Are Associated With Activation of Coagulation.

Patients undergoing liver transplantation have complex changes in their hemostatic system, and the net effect of these changes appears to be a “rebalanced” hemostatic profile. Recently, a process called NETosis in which a neutrophil expels DNA and proteins that form a weblike structure, has been described as a mechanism of pathogen entrapment. Increasing evidence suggests a pivotal role for neutrophil extracellular traps (NETs) and their main component, cell‐free DNA (cfDNA), in activation of coagulation. Because liver transplantation is associated with substantial (hepatocyte) cell death and intrahepatic neutrophil accumulation, NETs might play an important role in the hemostatic balance during liver transplantation. Here, we determined markers for NETs in the plasma of patients undergoing a liver transplantation and examined their association with activation of coagulation. Markers for NETs and markers for activation of coagulation were determined in serial plasma samples taken from patients undergoing a liver transplantation (n = 21) and compared with plasma levels in healthy controls. We found perioperative increases of markers for NETs with levels of cfDNA and nucleosomes that peaked after reperfusion and myeloperoxidase (MPO)–DNA complexes that peaked during the anhepatic phase. CfDNA and nucleosome levels, but not MPO‐DNA levels, correlated with prothrombin fragment 1+2 and thrombin‐antithrombin complex levels, which are established markers for activation of coagulation. Neutrophils undergoing NETosis were observed by immunostainings in postreperfusion biopsies. In conclusion, although NETosis occurs during liver transplantation, the majority of circulating DNA appears to be derived from cell death within the graft. The perioperative increases in cfDNA and nucleosomes might contribute to the complex hemostatic rebalance during liver transplantation.

A Study of Haemostatic Parameters in Patients with Philadelphia-Negative Myeloproliferative Neoplasms. Correlation with, Clinical, Laboratory, Molecular, and Treatment Characteristics

IntroductionPatients with Philadelphia-negative myeloproliferative neoplasms (PN-MPN) namely polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MF) are at a higher risk for arterial and venous thrombosis that constitute a major cause of morbidity and mortality. Global coagulation assays such as thromboelastography, may be more efficient to evaluate the patient's thrombotic risk. The aim of the present study was to examine the hemostatic profile of patients with PN-MPN and correlate it with clinical, laboratory, treatment, and molecular characteristics including mutational analysis of JAK2, MPL, CALR, and polymorphisms of poly(ADP ribose) polymerase (PARP1), since a correlation of specific mutations with PARP1 polymorphisms has been reported in the literature.Materials and methodsThe study included adult patients with a confirmed diagnosis of PN-MPN according to the revised 2016 WHO classification. A written informed consent was obtained from all patients. The presence of splenomegaly, vascular events, PN-MPN specific therapy, and anticoagulation treatment were recorded. All the patients were assessed with complete blood count, routine coagulation tests [PT, INR, aPTT and fibrinogen, D-Dimers analyzed with the automatic coagulation analyzer Sysmex (Siemens)], platelet function performed with PFA-100 (COL, EPI, ADP), and global hemostatic potential assessed with ROTEM® Tromboelastometry (EXTEM), recording clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), lysis index at 30 (LI30) and 60 (LI60) minutes, and α angle.Mutation profiles of JAK2, MPL and CALR were defined using peripheral blood DNA. JAK2 and MPL mutations were detected using a standard PCR and CALR mutations using an HRMA-PCR assay. The rs1136410/PARP-1 (V762A) single nucleotide polymorphism (SNP), was detected with an RFLP method using the enzyme AciΙ (New England Biolabs, USA) and the digestion products were evaluated by polyacrylamide gel electrophoresis.Statistical analysis was performed using IBM SPSS statistics, version 23.0 (IBM Corporation, North Castle, NY, USA).ResultsSeventy-four patients were included in the study (22 PV, 47 ET, 5 MF) with a median age of 63 years (25-87) and 68 healthy controls for the SNP/PARP1 study. At the time of sample collection, 71 (95.9%) patients were under treatment [hydroxyurea (HU), 57 (77.0%); anagrelide, 19 (25.7%); ruxolitinib, 9 (12.2%); interferon alpha, 2 (2.7%); an alkylating agent, 4 (5.4%)]. In terms of anticoagulation, 47 (63.5%) patients were on aspirin, 4 (5.4%) on clopidogrel, 7 (9.5%) on a combination of the two, 3 (4.1%) on a vitamin K antagonist, and 2 (2.7%) on a Xa-inhibitor. Twenty-two (29.7%) patients had abnormally high D-Dimers (>0,5mg/l). Nineteen (25.7%) patients had developed thrombosis after diagnosis (8, ischemic stroke; 4, coronary artery disease (CAD); 3, deep vein thrombosis (DVT); 1, symptomatic carotid stenosis; 2, a combination of stroke and CAD; 1, a combination of CAD and DVT). Among 69 patients who were not receiving anticoagulation, 5 (7,2%) had an abnormal CT, 4 (5,7%) had abnormal CFT, 3 (4,3%) had an increased α angle, and 18 (26%) had an increased MCF value.Women had shorter CFT, higher α angle, and higher MCF (p<0.05 for all parameters). Patients with ET had higher MCF compared to PV and MF. Patients with mutated JAK2, CALR, or MPL had higher WBC and shorter CFT (p<0.05).Patients receiving anagrelide or alkylating agents, had statistically significant shorter CFTs, higher α angles, and higher MCFs compared to the ones receiving HU.Among 54 patients taking aspirin COL-EPI was normal in 10. Among 11 patients taking clopidogrel COL-ADP was normal in 5, implying that the antiplatelet treatment may not be sufficient in certain cases. No correlations were found between PARP1 polymorphic status and any of the studied parameters, nor between patients and healthy controls.DiscussionGlobal assays such as thromboelastography are more useful than conventional hemostatic laboratory tests in depicting the hypercoagulable state in MPN. They may be useful in combination with other parameters such as the mutational status in identifying patients with MPN at higher risk for thrombosis and guide clinicians for the type of treatment (both cytoreductive and anticoagulants). Tests of platelet function assessment may help the clinicians adjust the type and dose of antiplatelet therapy. DisclosuresNo relevant conflicts of interest to declare.

DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis

AbstractMany hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we performed European and African ancestry–specific meta-analyses which were then combined via a random effects meta-analysis. For all other measures we could not estimate ancestry-specific effects and used a single fixed effects meta-analysis. We found that 1-year higher extrinsic epigenetic age as compared with chronological age was associated with higher fibrinogen (0.004 g/L/y; 95% confidence interval, 0.001-0.007; P = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P = 6.6 × 10−5) concentrations, as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms, we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene (SERPINE1) and the 3 fibrinogen subunit-encoding genes (FGA, FGG, and FGB) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a procoagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription.

Hemostatic profile under fluid resuscitation during rivaroxaban anticoagulation: an in vitro survey.

Uncontrollable bleeding is the leading cause of death in traumatically injured patients. The extent to which direct factor Xa inhibitors interfere with the applied resuscitation measures is presently unknown. In this study, we investigated the effect of the resuscitation fluids saline, albumin, fresh frozen plasma (FFP) and solvent/detergent (S/D)-treated plasma, fibrinogen concentrate, prothrombin complex concentrate (PCC), and combinations thereof on the hemostatic profile of rivaroxaban-anticoagulated whole blood and plasma. We used rivaroxaban-spiked whole blood and plasma from healthy donors, as well as plasma from patients on rivaroxaban, and mimicked a resuscitation approach in a 50% plasma dilution setting. Thromboelastography, thrombin generation, and fibrin generation clot lysis test were assessed using tissue factor to initiate coagulation and tissue plasminogen activator to induce clot lysis. Rivaroxaban resulted in a hypocoagulant state that remained largely unaltered upon subsequent 50% dilution with S/D-treated plasma or FFP. Using S/D-treated plasma as a diluent, clot stability decreased due to its low α2 -antiplasmin. Dilution with saline and albumin induced a profibrinolytic state and further deteriorated the impaired hemostatic potential of rivaroxaban-anticoagulated blood, even after PCC and fibrinogen support. Combined use of plasma (either FFP or S/D treated) and PCC, however, considerably improved both coagulation and clot stability. In the setting of rivaroxaban anticoagulation and major blood loss, transfusing plasma together with PCC may provide the most effective resuscitation approach with the notion that additional antifibrinolytic drug support (e.g., tranexamic acid) is likely required.

Haemostatic functions and metabolic profile of subclinical hypothyroid and hypothyroid patients.

Objectives: Both hypercoagulable and hypocoagulable states have been proposed for hypothyroidism, whether in overt or subclinical spectrum. The status of haemostatic functions, metabolic profile and their relationship in hypothyroid disorders need to be evaluated.Methods and Material: This prospective case control study was undertaken in 30- 50 years old female subclinical and hypothyroid patients. Haemostatic functions like bleeding time (BT), clotting time (CT), prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count and metabolic parameters like plasma glucose and lipid levels and clinical variables like blood pressure and body mass index were noted and compared. In addition the strength of correlation of TSH, T4, T3, lipid profile with the haemostatic functions was evaluated.Results: Both groups of patients were obese, normotensive with normal haemostatic parameters. The platelet count correlated with TSH in subclinical hypothyroid patients and with T4 levels in hypothyroid patients. Although within normal range, total cholesterol and LDL cholesterol levels were higher and postprandial plasma glucose (PPPG) levels lower in hypothyroid patients compared to subclinical hypothyroid patients. A positive correlation was seen between TSH and LDL, PPPG levels, between fT3 and BMI, and also of antiTPO with total cholesterol, LDL, Fasting plasma glucose (FPG) in hypothyroid patients. The BMI was negatively associated with fT3 levels in subclinical hypothyroid patients.Conclusion: This study found normal haemostatic and metabolic functions in both subclinical and hypothyroid patients. Although within normal range, hypothyroid patients had higher total and LDL cholesterol. TSH and antiTPO levels correlated with LDL levels in these patients. Correlation of platelet count with TSH in subclinical hypothyroid and T4 levels in hypothyroid patients advocate a difference in mechanism involved. Therefore it can be connoted that thyroid status influences metabolic profile, and platelet count.Bangladesh Journal of Medical Science Vol.17(4) 2018 p.532-536

Comprehensive analysis of haemostatic profile depending on clinicopathological determinants in breast cancer patients.

Thrombosis is one of the leading causes of mortality in cancer patients. The aim of the study was to evaluate the concentrations and activities of selected haemostatic parameters in the plasma of patients diagnosed with breast cancer (BrCa) and to make an attempt at finding associations with their levels and selected clinicopathological factors; clinical classification, histological grading, and molecular subtype of BrCa. The study involved 145 Caucasian ethnicity women. Eighty-five women aged 45–66 with primary BrCa without distant metastases (M0). Inclusion criteria were as follows: histopathological examination confirming the diagnosis of primary BrCa, without previous radiotherapy and chemotherapy. The control group consisted of 60, post-menopausal women, aged 45–68. Haemostatic profile expressed by concentrations and activities of tissue factor (TF) and its inhibitor (TFPI) as well as concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were measured applying immunoassay techniques. A significantly higher concentration of PAI-1 was noted in patients with BrCa localized in the left breast. We observed significantly lower activity of TFPI and significantly higher concentration of PAI-1 in the group of patients with invasive ductal carcinoma as compared with invasive lobular carcinoma. A significantly higher concentration of t-PA in patients with pT2 BrCa in relation to pT1 cases was noted. Based on comprehensive analysis of haemostatic profile depending on clinicopathological features, we suggest that haemostatic parameters play crucial roles in invasion and metastases of malignant tumours.

Telangiectatic Matting is Associated with Hypersensitivity and a Bleeding Tendency

The aim was to investigate the pathogenesis of telangiectatic matting (TM) and identify possible risk factors. This study had two parts. The clinical records of consecutive patients were retrospectively analysed to identify risk factors for TM. In the second part, the haemostatic and coagulation profile of the subset of patients with TM were analysed and compared with controls using standard coagulation tests, platelet function and a global assay of coagulation (rotational thromboelastometry, ROTEM). In 352 consecutive patients presenting to a phlebology practice, 25 patients had TM (7.1%). All 25 patients were female with the median age of 45 (27-57) years. A comprehensive medical history was taken. Among 27 possible risk factors assessed, statistically significant associations included recurrent epistaxis, easy bruising, hypersensitivity (eczema, hives, hay fever, and rhinitis), previous treatment with sclerotherapy or endovenous laser for lower limb veins, and a family history of telangiectasias. Variables not associated with TM included oral contraceptive intake, hormone replacement therapy, and age. The haemostatic and coagulation profile of 12 patients (6 male and 6 female) with TM did not differ significantly from those without TM. TM is associated with both hypersensitivity and a bleeding tendency. This study revealed no significant increase in the incidence of haemostatic abnormalities in patients with TM compared with the control group. Given the significant association with hypersensitivity disorders, the underlying mast cell hyper-reactivity may contribute to both hypersensitivity and a bleeding tendency and predispose patients to TM.

Hemostatic profile and safety of pooled cryoprecipitate up to 120 hours after thawing.

AABB standards state that cryoprecipitate should be transfused within 4 to 6 hours after thawing. We evaluated coagulation factor levels and sterility of thawed pooled cryoprecipitate to assess whether shelf life can be safely extended. Donor cryoprecipitate pools (n = 20, 10 group A, 10 group O) were held at ambient temperature and sampled at 0, 4, 8, 24, 48, 72, 96, and 120 hours post-thawing for fibrinogen, Factor (F)VIII, and von Willebrand factor (vWF) levels. Samples were tested at 0 and 120 hours for sterility (BacT/Alert system). Sixty additional cryoprecipitate pools were evaluated after 72 hours. Longitudinal differences in component levels were determined by linear fixed-effects regression. Group O cryoprecipitate had significantly lower FVIII (p = 0.002) and vWF activity (p = 0.006) compared to group A at 0 hours, but were not statistically different in fibrinogen levels (p = 0.33). Fibrinogen levels were stable over 5 days: 501 ± 81 mg/unit (mean ± standard deviation) at 0 hours to 506 ± 102 mg/unit at 120 hours (p = 0.73). Similarly, there was no decline in vWF activity: 200 ± 53 IU/unit at 0 hours to 209 ± 57 IU/unit at 120 hours (p = 0.084). The FVIII activity significantly declined on average by 9.6 IU (95% confidence interval, 5.5-13.8) between 0 hours (111 ± 33 IU/unit) and 120 hours post-thaw (101 ± 33) (p < 0.001). No organisms were detected when cryoprecipitate pools were cultured at 0 hours, but at 120 hours Staphylococcus epidermidis was identified from one pool, potentially a contaminant introduced during repeated sampling. No cultures were positive among the 60 additional cryoprecipitate pools assessed at 72 hours. Extended cryoprecipitate storage at ambient temperature did not affect fibrinogen levels over 120 hours. Sterility of products held at ambient temperature for an extended period of time could be assessed by secondary culture.

Comparison of zone 3 Resuscitative Endovascular Balloon Occlusion of the Aorta and the Abdominal Aortic and Junctional Tourniquet in a model of junctional hemorrhage in swine

BackgroundTraumatic injuries to the pelvis and high junctional injuries are difficult to treat in the field; however, Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) and the Abdominal Aortic and Junctional Tourniquet (AAJT) constitute two promising treatment modalities. The aim of this study is to use a large animal model of pelvic hemorrhage to compare the survival, hemostatic, hemodynamic, and metabolic profile of both techniques. MethodsYorkshire swine (n = 10, 70-90 kg) underwent general anesthesia, instrumentation, and surgical isolation of the femoral artery. Uncontrolled hemorrhage was initiated by an arteriotomy. Animals were randomly allocated to either REBOA or AAJT. Following completion of device application, both groups received a 500 mL Hextend bolus. After 1 hour, the injured femoral artery was ligated to simulate definitive hemostasis followed by a second Hextend bolus and device removal. Animals were observed for two more hours. Physiological data were collected throughout the experiments and compared between groups. ResultsBoth techniques achieved 100% hemostasis, and all animals survived the entire experiment except one in the REBOA group. During the hour treatment phase, the AAJT group had a higher mean arterial pressure than the REBOA group (59.9 ± 16.1 versus 44.6 ± 9.8 mm Hg, respectively; P < 0.05). The AAJT-treated group had higher lactate levels than the REBOA-treated group (4.5 ± 2.0 versus 3.2 ± 1.3 mg/dL, respectively; P < 0.05). ConclusionsDespite their mechanistic differences, both techniques achieved a similar hemostatic, hemodynamic, and metabolic profile. Some differences do exist including lactate levels and blood pressure.

Evaluation of lipid profile, high-sensitivity C-reactive protein and D-dimer in users of oral contraceptives of different types

ABSTRACT Introduction: The use of oral contraceptives increases women's risk of developing cardiovascular and thromboembolic diseases, due to alterations in hemostatic and lipid profile. Objectives: Analyze the association between the use of different types of oral contraceptives with lipid profile and levels of serum high-sensitivity C-reactive protein (hsCRP) and plasma D-dimer. Methods: One hundred fifty-four participants were divided into the following groups: control nonusers (n = 41), medium-dose users (n= 32), third-generation low-dose users (n = 40), and fourth-generation low-dose users (n = 41). Triglycerides and total cholesterol serum levels were determined by colorimetric enzymatic method; high-density lipoprotein (HDL) cholesterol levels, by precipitation method; low-density lipoprotein (LDL) cholesterol levels, by Friedewald equation; hsCRP levels, by immunoturbidimetric method; and D-dimer levels, by fluorescence immunoassay. Results: Oral contraceptive users had higher serum levels of triglycerides, total cholesterol, HDL cholesterol (HDL-C), HDL/LDL index and hsCRP compared to controls. Medium-dose users had higher D-dimer plasma levels than controls and higher triglycerides serum levels than low-dose users. Triglycerides, hsCRP and D-dimer were positively correlated to each other. Conclusion: The use of combined oral contraceptives was associated with an unfavorable lipid profile and a chronic subclinical inflammation, with atherogenic potential. Furthermore, medium-dose contraceptives induced a higher thrombogenic potential, since they were associated with increased D-dimer levels in comparison to low-dose ones.

Posterior reversible encephalopathy syndrome following blood transfusion in a patient with factor X deficiency: Is it an unusual systemic manifestation of an adverse transfusion reaction?

Adverse neurological transfusion reactions including posterior reversible encephalopathy syndrome (PRES) following blood transfusion are rare. Our case an 18-year-female with known Factor X deficiency with menorrhagia developed severe hypertension, followed by generalised tonic clonic convulsions apparently after blood component transfusion. She had earlier received 4 units of red blood cells (RBC) for anaemia and 10 units of fresh frozen plasma (FFP) for menorrhagia (with prolonged PT and APTT) within short span of time at another hospital. There was no history of hypertension, convulsions, any cardiovascular, renal or neurological disease before transfusion. The clinical features and magnetic resonance imaging findings led to the diagnosis of PRES. Abnormal electroencephalogram and a hypercoagulable haemostatic profile on thromboelastography along with derangement in blood glucose and liver function tests were also observed. Patient responded well to the anticonvulsants and antihypertensive agents prescribed and was discharged in a stable condition. Our patient had a systemic transfusion reaction involving predominantly neurological system, however, cardiovascular, hepatic, haemostatic and endocrine systems were also affected. This case is unusual being the first report of PRES occurring in a patient with factor X deficiency presenting with an array of clinical and laboratory features which have not been reported in earlier studies involving PRES. Presumably the initial aggressive red cell transfusion to treat anaemia initiated the crisis and further large volumes of transfused FFP contributed to this adverse transfusion reaction in our case. Clinicians and Transfusion Medicine specialists should be aware about this uncommon clinical entity.

Neurosurgical applications of viscoelastic hemostatic assays.

Patients taking antithrombotic agents are very common in neurosurgical practice. The perioperative management of these patients can be extremely challenging especially as newer agents, with poorly defined laboratory monitoring and reversal strategies, become more prevalent. This is especially true with emergent cases in which rapid reversal of anticoagulation is required and the patient's exact medical history is not available. With an aging patient population and the associated increase in diseases such as atrial fibrillation, it is expected that the use of these agents will continue to rise in coming years. Furthermore, thromboembolic complications such as deep venous thrombosis, pulmonary embolism, and myocardial infarction are common complications of major surgery. These trends, in conjunction with a growing understanding of the hemostatic process and its contribution to the pathophysiology of disease, stress the importance of the complete evaluation of a patient's hemostatic profile in guiding management decisions. Viscoelastic hemostatic assays (VHAs), such as thromboelastography and rotational thromboelastometry, are global assessments of coagulation that account for the cellular and plasma components of coagulation. This FDA-approved technology has been available for decades and has been widely used in cardiac surgery and liver transplantation. Although VHAs were cumbersome in the past, advances in software and design have made them more accurate, reliable, and accessible to the neurosurgeon. VHAs have demonstrated utility in guiding intraoperative blood product transfusion, identifying coagulopathy in trauma, and managing postoperative thromboprophylaxis. The first half of this review aims to evaluate and assess VHAs, while the latter half seeks to appraise the evidence supporting their use in neurosurgical populations.

Fibrinogen deficiency in a dog - a case report

BackgroundAmong coagulation disorders, primary fibrinogen deficiency is very rare in dogs. It is divided into hypofibrinogenemia, afibrinogenemia and dysfibrinogenemia. Afibrinogenemia has been described in three dogs. There are, however, no published case reports of primary hypofibrinogenemia in dogs.Case presentationA 1.5 year-old male German Pointer dog was evaluated for a locked-jaw syndrome associated with eye protrusion which appeared after a minor head trauma. Three months before the trauma, a persistent increase in coagulation times was detected by the referring veterinarian after a strong suspicion of snake envenomation. Apart for the primary complaint, physical examination was normal. A complete hemostatic profile revealed a moderately increased prothrombin time, activated partial thromboplastin times and a dramatically decreased fibrinogen concentration (0.34 g/L, reference interval [1.3–4.8 g/L]). Platelet count, plasma D-dimers and antithrombin, were all within the reference intervals and not consistent with a disseminated intravascular coagulation. Other possible causes of hypofibrinogenemia such as chronic hemorrhage and liver failure were excluded by laboratory work-up and imaging studies. Finally, antifibrinogen circulating anticoagulants were excluded using a dilution of citrated plasma from the pooled plasma of healthy dogs. These results supported a diagnosis of congenital fibrinogen deficiency and secondary retrobulbar hematoma and/or cellulitis. The dog’s condition improved rapidly after symptomatic treatment with corticosteroids and antibiotics. At the 1 year follow-up, the dog was clinically normal but a persistent hypofibrinogenemia (≤ 0.8 g/L) remained.ConclusionsVarious clinical presentations may occur in canine primary hypofibrinogenemia which should be included in the list of coagulation disorders. Diagnosis should include fibrinogen determination by coagulometric and non-coagulometric methods to differentiate from dysfibrinogenemia. There is no specific treatment but care should be taken to prevent bleeding and trauma. Emergency management of bleeding episodes with cryoprecipitate is the treatment of choice.

Blood coagulation system in patients with chronic kidney disease: a prospective observational study

ObjectivesThromboembolic events are the major factor affecting the prognosis of patients with chronic kidney disease (CKD). Haemostatic alterations are possible causes of these complications, but their roles remain poorly characterised....