Hemostatic Status Research Articles

Haemostatic, fibrinolytic and inflammatory profiles in West Highland white terriers with canine idiopathic pulmonary fibrosis and controls

BackgroundCanine idiopathic pulmonary fibrosis (CIPF) is a progressive interstitial lung disease mainly affecting old West Highland white terriers (WHWTs). The aetiology of CIPF is currently unknown and pathogenesis poorly understood. A genetic basis is strongly suspected based on the breed predisposition. CIPF shares clinical and pathological features with human IPF. In human IPF, coagulation disorders favouring a local and systemic pro-thrombotic state have been demonstrated in association with disease severity and outcome. The aim of this study was to compare the systemic haemostatic, fibrinolytic and inflammatory profiles of WHWTs affected with CIPF with breed-matched controls (CTRLs). Additionally, data collected in both groups were interpreted with regard to the reference intervals (when available) to assess possible pro-thrombotic features of the WHWT breed that may be related to CIPF predisposition. A total of 14 WHWTs affected with CIPF and 20 CTRLs were included.ResultsWHWTs affected with CIPF had prolonged activated partial thromboplastine time in comparison with CTRLs (12.2 ± 0.9 s vs. 11.5 ± 0.7 s, P = 0.028), whereas results obtained in both groups were all within reference ranges. There was no significant difference between groups for the other factors assessed including plasmatic concentrations of fibrinogen, D-dimers concentration, antithrombin III activity, protein S and protein C activities, anti-factor Xa activity, activated protein C ratio, serum C-reactive protein concentration, and rotational thromboelastometry indices. Platelet count and plasmatic fibrinogen concentration were found to be above the upper limit of the reference range in almost half of the WHWTs included, independently of the disease status.ConclusionsResults of this study provide no clear evidence of an altered systemic haemostatic, fibrinolytic or inflammatory state in WHWTs affected with CIPF compared with CTRLs. The higher platelet counts and fibrinogen concentrations found in the WHWT breed may serve as predisposing factors for CIPF or simply reflect biological variation in this breed.

ЗВ'ЯЗОК ПАРАМЕТРІВ ТРОМБОЕЛАСТОГРАФІЇ ЗПОКАЗНИКАМИ ТЕСТІВ ДОСЛІДЖЕННЯ ГЕМОСТАЗУУ ХВОРИХ НА ГЕМОФІЛІЮ А ПІД ЧАС ПРОФІЛАКТИЧНОГО ЛІКУВАННЯ

Background: In order to control the treatment of haemophilia patients, classical coagulation methods (APTT, FVIII (IX)) and global tests are used. One of the tests for a comprehensive coagulation assessment is thromboelastography (TEG), which can provide immediate results and reflect the hemostatic status of the patient during therapy. Some of the parameters obtained from the TEG can be compared with the coagulation tests since they describe similar processes of coagulation. Purpose: To carry out a correlation analysis of TEG parameters with coagulation test parameters to determine the role of TEG in the control of prophylactic treatment and the development of inhibitors in patients with severe haemophilia A. Materials and methods: 9 haemophilia A patients were treated with 45 ± 5 IU/kg of FVIII of body weight twice a week prophylactically an incremental recovery test (IR) at a dose of 60 ± 5 IU/kg body weight was performed. Prior to and after administration, TEG was performed and the PT, APTT, fibrinogen, FVIII, FVIII:Ag, vWF:Ag and the platelet count were measured. The possible dependencies of 10 TEG parameters (R, K, α-Angle, MA, TMA, SI, SP, G, LY30, TPI/c) and coagulation tests results were analyzed. Results: Significant direct correlation of the R and SP on the PT and APTT was found (r > 0.71) prior to the administration of the FVIII concentrate. The negative average correlation between R and FVIII:Ag (r = ‑0.56) was established. The elongation of the PT and APTT and the decrease in the activity of FVIII:Ag causes a decrease in the total hemostatic potential of the SI in the direction of hypocoagulation (r = 0.75). Prior to administration of the calculated dose, the concentration of MA, TMA and α-Angel inclination strongly and directly depends on the level of vWF:Ag and platelet count (in all cases r > 0.7). After administration of the FVIII concentrate in haemophilia A patients, a significant positive correlation between the response time R and the APTT (r = 0.64) was found. The growth of the CІ coagulation index is associated with an increase in the level of FVIII: Ag (r = 0.75) and a shortening of the APTT (r = -0.76). Other dependencies between TEG parameters and hemostatic tests have not been established. Conclusion: Correlation of TEG parameters and results of traditional coagulation tests characterized similar processes of coagulation and was revealed in haemophilia A patients on prophylactic treatment. For R, SI, SP depending on the values of the PT, APTT, FVIII: Ag, the end point is coagulation. MA, TMA, α-Angel depend on the level of vWF: Ag and platelet count which reflects the initiation of haemostasis and the strength of clot. TEG fully reflects the changes in hemostasis, so thromboelastography can be successfully applied to control the treatment and the development of FVIII (IX) inhibitors in hemophilia patients.

Application of thrombelastography in primary total knee and total hip replacement: a prospective 87 patients study.

: Thrombelastography (TEG) parameters and prothrombin time (PT), activated partial thromboplastin time (APTT) are compared and analysed. According to change of TEG parameters and assessment of haemostatic state of each patient, we try to explore the feasibility of individualized anticoagulant therapies. 87 people with hip or knee diseases awaiting arthroplasty were recruited. Haemoglobin levels and TEG parameters including R, K, α-angle, maximum amplitude, coagulation index were assessed in perioperative period. PT and APTT were assessed preoperatively. For 65 patients with normal TEG parameters, PT and APTT, we use tranexamic acid (TXA) to reduce blood loss during operation. As hypercoagulability group, 12 patients awaiting unilateral total knee arthroplasty with hypercoagulable state assessed by TEG parameters or risks for venous thromboembolism received daily 10-mg rivaroxaban until 24 h preoperatively and did not receive TXA during operation. All patients received intravenous administration of argatroban after 8 h postoperatively until day 3 and oral administration of rivaroxaban (10 mg) subsequently to prevent deep vein thrombosis or/and pulmonary embolism until 35 days postoperatively. TEG parameters have significant relationships with fibrinogen, platelet and APTT. The number of patients with abnormal haemostatic state assessed by TEG parameters is higher than that assessed by PT, APTT. TEG show hypercoagulability develops throughout perioperative period. There was no significant difference in haemoglobin concentration between hypercoagulability group and normal group in patients receiving unilateral total knee arthroplasty. TEG have higher sensitivity of perioperative abnormal haemostatic state than PT, APTT in primary arthroplasty. For patients with hypercoagulability, individualized anticoagulant therapies such as preoperative administration of rivaroxaban and not using TXA in operation is safe and effective.

Breast tumour size as a predictor of hemostatic system status and endothelial function in dogs

The high level of morbidity of dogs from mammary gland tumours and deficiencies in the pathogenesis give relevance to study of the disorders of the hemostatic system for predicting the neoplasia process. Our research concerned the determination of markers of the hemostatic system and endothelial function at different sizes (≤ 2, 5–7 and >10 cm) of benign (n = 28) and malignant (n = 27) breast tumours in dogs, taking into account their histological structure. The progression of the tumour process was accompanied by a 1.24–1.81 times increase in the fibrinogen content in the benign forms and 1.39–2.38 times in malignant against the background of progressive excess accumulation of soluble fibrin. The results of coagulation tests indicate that the increase in blood coagulation, which correlates with the magnitude of tumours, occurred mainly externally. In malignant neoplasms reliable, compared to clinically healthy dogs, reduction of total fibrinolytic activity occurred due to deficient inhibition of tissue plasminogen activator by 1.62–2.03 times. Increase in the size of benign neoplasms was accompanied by increased activity of the α1-inhibitor of proteinases, and in malignant – only in tumours of the size of 5–7 cm, against the background of its decrease in dogs with small and giant neoplasia. The progression of the disease was characterized by an increase in the content of α2-macroglobulin in benign lesions from 1.19–1.24 times, malignant – from 1.25–2.03 times. At the same time, there was a deepening of oxidative stress, as evidenced by the excess accumulation in the blood of malondialdehyde by 1.29–1.70 times in benign tumours, and 1.58–2.73 times in malignant. Regardless of the pathomorphologic form, the magnitude of the neoplasia foci is directly correlated with excess accumulation of nitric oxide and the level of hypoproteinemia, and vice versa – the content of ceruloplasmin. Further research should be undertaken to study the hemostatic status in certain nosological forms of breast tumours in dogs, which will improve the diagnosis and development of effective treatment protocols.

BASELINE PLASMA THROMBOELASTOGRAPHY IN KEMP'S RIDLEY (LEPIDOCHELYS KEMPII), GREEN (CHELONIA MYDAS) AND LOGGERHEAD (CARETTA CARETTA) SEA TURTLES AND ITS USE TO DIAGNOSE COAGULOPATHIES IN COLD-STUNNED KEMP'S RIDLEY AND GREEN SEA TURTLES.

Cold-stunning in sea turtles is a frequent natural cause of mortality and is defined as a hypothermic state due to exposure to water temperatures <12°C. Derangements of biochemistry and hematology data by cold stunning have been well documented, although the effects on coagulation have not yet been investigated. The objectives of this study were to characterize the hemostatic state of non-cold-stunned sea turtles and to compare cold-stunned sea turtles at admission and after successful rehabilitation via a sea turtle-specific thromboelastography (TEG) protocol. TEG enables evaluation of the entire coagulation process, and the methodology has recently been established in sea turtles. Initially, 30 wild and apparently healthy sea turtles were sampled as controls: loggerhead sea turtles (Caretta caretta), n =17; Kemp's ridley sea turtles (Lepidochelys kempii), n = 8; and green turtles (Chelonia mydas), n = 5. In addition, paired TEG samples were performed on 32 Ch. mydas and 14 L. kempii at admission and prerelease after successful rehabilitation from cold stunning. Statistically significant differences in reaction time, kinetics, angle, and maximum amplitude parameters in L. kempii and Ch. mydas species demonstrated that the time taken for blood clot formation was prolonged and the strength of the clot formed was reduced by cold stunning. These findings indicate that cold stunning may cause disorders in hemostasis that can contribute to the severity of the condition. Early diagnosis of coagulopathies in the clinical assessment of a cold-stunned sea turtle may influence the treatment approach and clinical outcome of the case.

Coagulation and Circulating Heparin Profile in Patients with End‐Stage Renal Disease Undergoing Maintenance Hemodialysis

IntroductionUnfractionated heparin is widely used as an anticoagulant for maintenance hemodialysis in end‐stage renal disease (ESRD) patients. Since these patients are administered with heparin repeatedly throughout treatment, it is hypothesized that detectable circulating levels of heparin may be present in their blood 48 hours post‐dialysis session. Changes in the profile of coagulation factors for the intrinsic and extrinsic pathway may also be associated with repeated heparization and can be measured using global clotting assays. The profiling of these parameters may provide the hemostatic status of patients in reference to circulating residual heparin in the pre‐dialysis blood samples.Materials/ MethodsThis study included 95 patients with ESRD undergoing maintenance hemodialysis, which was administered 3 times per week in 48‐hour intervals. Citrated blood samples were collected, centrifuged, and platelet‐poor plasma was retrieved. Plasma samples were analyzed utilizing clot‐based methods including activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT). Employing a chromogenic assay, the circulating levels of heparin in each patient were measured. All of these samples were also analyzed for thrombin generation capacity using calibrated automated thrombogram (CAT, Diagnostica Stago. Paris, France).ResultsIn the clotting assays, prothrombin time was elevated (16.4 ± 20.3 sec.) in comparison to the normal control (11.1 ± 2.1 sec.). Activated partial thromboplastin time was also prolonged (43.09 ± 43.1 sec.) when compared to normal human plasma (32.3 ± 4.2 sec.). The thrombin time values were also higher (44.6 ± 83.1 sec.) in comparison to normal (11.2 ± 2 sec.). Circulating heparin levels, measured by anti‐Xa methods, were found to be 0.11 ± 0.21 U/ml and anti‐IIa levels being 0.25 ± 0.27 U/ml. The anti‐Xa/anti‐IIa ratio were determined to be 0.43. In the thrombin generation assay, the ESRD samples showed wide variation and a lowered thrombin generation value (107 ± 55.2 nM) in comparison to normal control (185 ± 16.5 nM).DiscussionThese results suggest patients undergoing maintenance hemodialysis exhibit a mild hypocoagulable state as determined by PT and aPTT methods. Although both methods demonstrated wide variation, this prolongation indicated defective intrinsic and extrinsic pathways. Moreover, the thrombin time elevation is suggestive of defective common pathway and the presence of circulating heparin. The circulating levels of heparin were lower in anti‐Xa compared to anti‐IIa, suggesting the presence of higher molecular weight components of heparin. This is likely due to impaired clearance of higher molecular weight heparin components caused by maintenance hemodialysis. The decreased thrombin generation observed in these patients may be partly due to the defects in the coagulation process and presence of heparin in the ESRD patients.Support or Funding InformationNAThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The hemostasis system in children with hereditary spherocytosis

IntroductionPatients with hereditary spherocytosis (HS) are characterized by having an increased risk for thrombosis. An early manifestation of thrombotic complications can occur even in childhood, especially after surgery. Hypercoagulability can be associated with hemolytic crises. AimThe aim of this study was to investigate the hemostatic state in children with HS using global hemostasis assays. MethodsThe hemostatic status of 62 children (38 boys and 24 girls; age range: 0.5 to 17 years) with HS during and without hemolytic crisis was assessed using clotting times (APTT, TT, and PR), fibrinogen and D-dimer levels, and global hemostasis, thromboelastography (TEG) and thrombodynamics (TD) assays. One hundred and two healthy children undergoing annual medical examination were enrolled as a control group. ResultsTEG and TD parameters were increased in the children with HS compared to the control group (60 ± 5 mm vs. 53 ± 4 mm, p < 0.05 for TEG maximum amplitude; 28 ± 3 μm/min vs. 24 ± 2 μm/min, p < 0.05 for TD clot growth rate), while APTT, TT and PR were not significantly different between the two groups. Patients with HS were divided into 2 groups: those during hemolytic crisis (28 patients) and those without hemolytic crisis (34 patients). TEG and TD parameters were increased in those during hemolytic crisis compared to the steady state HS group (62 ± 5 mm vs. 57 ± 4 mm, p < 0.05 for TEG maximum amplitude; 31 ± 4 μm/min vs. 26 ± 3 μm/min, p < 0.05 for TD clot growth rate). The D-dimer levels were increased in 4 HS patients, for whom the activation of blood clotting was noted. Fibrinogen levels were decreased in patients with HS compared to the control group (2.1 ± 0.4 mg/ml vs. 2.6 ± 0.4 mg/ml, p < 0.05). Other tests were within the reference ranges for both groups. ConclusionsThe global hemostasis tests TEG and TD revealed hypercoagulability in patients with HS. More dramatic changes were observed in patients experiencing a hemolytic crisis.

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.

Uzrok krvarenja iz gornjih partija digestivnog trakta i hitna gastroskopija u Urgentnom Centru KC Kragujevac

Introduction: Digestive tract bleeding is a clinical problem that requires hospitalization. Hemorrhages from the upper parts of the digestive system have an incidence of 150/100000 persons per year and are the reason for 1.5% of all emergency hospitalizations. The most common cause of bleeding is gastroduodenal ulcer and erosion in three quarters of cases. Endoscopic haemostatic and gastric acidity status are the most important in the treatment of patients. Aim: To analyze the causes of bleeding from the upper parts of digestive tract and the justification for the urgent gastroscopy. The study was conducted at the Clinical Center Kragujevac in Kragujevac, Serbia. Methods: The study included patients (200) who reported to the emergency room of the Emergency Medicine Center with the clinical picture of bleeding from the upper parts of the digestive tract. Results: Most patients had ulcerative changes at gastric level (58.6%). The most common symptom was melena present in 152 patients. Endoscopic therapy was administered to 44 patients, with 38 patients (86.4%) resulting in arresting bleeding. Conclusion: Hemorrhages from the upper parts of the digestive tract are most commonly caused by peptic ulcers, more common in older, male patients. The first form of diagnosis and therapy is endoscopy, with an efficacy greater than 70%.

A prediction model for successful anticoagulation in cirrhotic portal vein thrombosis.

Portal vein thrombosis (PVT) is a common complication in cirrhosis, and when complete, it increases morbidity and mortality in liver transplant candidates. The aim of the study was to assess the hemostatic status, as well as clinical characteristics of thrombus and patients, as predictors of therapeutic efficacy of anticoagulation for the treatment of PVT in cirrhotics. Patients with cirrhosis consecutively treated for PVT with enoxaparin were enrolled. All patients underwent evaluation of coagulation status and thrombophilia screening. Thrombus characteristics and extension were evaluated at baseline and during follow-up. Anticoagulation was continued until recanalization or up to 12 months. Variables correlated with the response to anticoagulation were used to create a predictive score that was validated in an external multicenter cohort. A total of 65 patients were included and had partial PVT in most cases (72%). Treatment with enoxaparin resulted in an overall response rate of 66% (43/65) after a median time of 4.4 months and 76% (33/43) within the first 6 months. At multivariate analysis, efficacy of anticoagulation correlated with the severity of liver disease, complete verus partial PVT, age of the thrombus, and time interval from treatment start (<6 months). The areas under the curve of the statistical model for predicting the response to anticoagulation were 0.84 and 0.76 for the training (n=65) and validation (n=60) cohorts, respectively. Early diagnosis and early treatment are key factors for the successful management of PVT in cirrhosis, so that screening of PVT and prompt start of anticoagulant treatment should be mandatory.

Effects of Direct Oral Anticoagulants on Quality of Life During Periprocedural Management for Dental Extractions

Direct oral anticoagulants (DOACs) have many advantages over warfarin regarding periprocedural management for dental extractions. They avoid the need to assess and possibly adjust warfarin therapy to achieve appropriate hemostatic status before and after extraction. The present study evaluated the real-life data regarding quality of life (QoL) and burden for patients with atrial fibrillation receiving long-term treatment with warfarin or DOACs during periprocedural management for dental extraction. We implemented a multicenter study. The sample was composed of 205 patients who had been receiving long-term anticoagulation treatment with warfarin (n=133) or DOACs (n=72). The Duke Anticoagulation Satisfaction Scale (DASS) was used to assess the QoL. Periprocedural management for dental extraction was recorded using the questions designed by us. Warfarin created a significantly greater burden for patients during periprocedural management for dental extraction compared with DOACs. The DASS results showed that the QoL of patients was significantly better for the DOAC group than for the warfarin group (score, 75.19±18.52 and 90.12±17.28, respectively; P=.0001). Of the patients in the DOAC group, 45 had used warfarin as their previous therapy and had undergone another tooth extraction while using warfarin. Of these patients, 91.1% chose DOACs as their anticoagulant of choice for dental extraction. The present findings suggest that DOACs have many advantages compared with warfarin regarding the reported QoL and periprocedural management of dental extraction.

Evaluation of EC50 of factor VIII as predictor of prophylaxis efficacy in patients with severe haemophilia A

Trough factor (F) VIII level is a not reliable bleeding risk indicator to predict prophylaxis efficacy in severe haemophilia A (SHA), therefore, accurate biomarkers are much needed. Thrombelastography (TEG) monitors both thrombin and clot formation addressing the global haemostatic status but its usefulness to tailor prophylaxis in haemophilia has been poorly evaluated. In this study, correspondence between individual pharmacodynamic/pharmacokinetic profile of FVIII and joint condition, physical activity and bleeding phenotype of SHA patients under prophylactic treatment was assessed. Nineteen SHA patients < 18 years old on long-term prophylaxis treatment with FVIII were studied in an observational cross-sectional study. Whole blood was withdrawn before FVIII administration and at five time-points after infusion for a TEG-based pharmacodynamic- and pharmacokinetic-study. Type of prophylaxis and joint condition at inclusion and physical activity as well as onset of treated spontaneous bleeding events in the previous two years were retrospectively assessed. Six patients had suffered at least one treated spontaneous bleeding event and were named as “bleeders”. The rest were named as “non-bleeders”. Only the half maximal effective concentration of FVIII (FVIII-EC50) for TEG parameters R-time, K-time and α-angle correlated with the bleeding phenotype being significantly higher in bleeders suggestive of a poorer response to FVIII. Poorer joint condition, trough FVIII levels or type of prophylaxis were not definitive predicting variables of bleeding phenotype. In conclusion, this study reveals FVIII-EC50 for the first time as a valuable biomarker to anticipate individual efficacy of prophylaxis in SHA.

Rutin (quercetin-3-rutinoside) modulates the hemostatic disturbances and redox imbalance induced by Bothrops jararaca snake venom in mice.

Snakebites are a major Collective Health problem worldwide. In Brazil, Bothrops jararaca snake venom (BjV) evokes hemostatic disturbances, bleeding manifestations, and redox status imbalance. Specific antivenom therapy, although efficacious to revert most snakebite-induced manifestations, is incapable of treating secondary manifestations, such as oxidative/nitrosative stress. Searching for new complementary therapies that could attenuate physiological derangements triggered by envenomation, we elected to test quercetin-3-rutinoside (rutin) by its potential as both a potent antioxidant and a hemostasis modulatory compound. The activity of rutin was evaluated both on the biological activities of crude BjV in vitro, and in vivo by the ability of rutin (14.4 mg/kg b.w.) to modulate hematological, hemostatic and redox status markers altered by BjV injection (1.6 mg/kg b.w., s.c.) in mice. In vitro, rutin failed to inhibit BjV-induced platelet aggregation and biological activities of major BjV enzymes (metalloproteinases, phospholipases A2, serine proteases, and L-amino acid oxidases). On the other hand, rutin attenuated local hemorrhage, and the increase in reactive species, prevented the fall in RBC counts and fibrinogen levels, diminished tail bleeding and shortened prothrombin time (PT) evoked by envenomation. Furthermore, rutin reduced tissue factor (TF) activity and altered the protein expression of TF in liver, lungs, heart and skin. In conclusion, the disturbances in redox status and hemostatic system induced by B. jararaca envenomation were modulated by rutin, suggesting it has a great potential to be used as an ancillary therapeutic agent for snakebites.

Hemostatic state augmented with platelet indices among Sudanese diabetic septic foot

BackgroundDiabetes mellitus is a very rampant metabolic disorder, particularly type II. It has many complications such as the septic foot. Diabetic septic foot (DSF) patients are at high risk for coagulation abnormalities as well as surgical hazards. Owing to the potential sequelae of coagulation and vascular abnormalities, this work aimed at studying the hemostatic state and platelet indices in diabetes type II patients with septic foot.MethodsA case-control study was conducted during the period from July to September 2017 at Dr. Awaad medical center, Red Sea State, Sudan. 57 diabetic patients with septic foot, aged between 17 and 78 years along with 57 non-diabetic subjects as control were enrolled. Sociodemographic data were collected using a structured questionnaire. Venipuncture blood was taken with necessary safety measures. Diabetes profile, coagulation studies as well as platelet indices were estimated. Data was analyzed using SPSS version 24.0 for windows. Ethical approval was considered and written consent from each participant was obtained.ResultsThe mean age of diabetic patients with septic foot and healthy controls were 48.49 ± 15.8 and 32.77 ± 14.0, respectively. The duration of the diabetes onset was 10.43 ± 9.5 years. Plasma prothrombin time (PT) value (12.61 ± 2.6 vs 13.67 ± 1.5, P < 0.009) was found to be significantly shorter in DSF compared to control. Plasma activated partial thromboplastin time (APTT) value was significant in diabetic septic foot (32.64 ± 5.2 vs 28.49 ± 4.13, P < 0.000), and thrombin time (TT) did not changed in DSF. Mean platelet volume (MPV), platelet distribution width (PDW), and platelet large cell ratio (P-LCR) values were significantly decreased in DSF compared to control (P < 0.013, 0.034, and 0.020, respectively). PDW values were positively correlated with PT, APTT, and D-Dimer (DD) (r = 0.28/p < 0.003, r = 0.29/p < 0.029, and r = 0.32/p < 0.016, respectively). FVIII activity (121.86 ± 174.4 vs 98.66 ± 31.83, P < 0.951) was insignificant with DSF, as the DD was also insignificant (P < 0.081).ConclusionDiabetes mellitus is associated with prothrombotic tendency. Hypercoagulable state in DSF is indicated by shortened PT finding. PDW is a manifesting evidence that proves the presence of more reactive and aggregable platelets in DSF patients.

Hemostasis during Extreme Exertion.

Exercise is protective against cardiovascular disease, but can also provoke sudden cardiac death, a phenomenon referred to as "the exercise paradox." Extreme exertion is known to induce a rebalanced hemostatic state by causing hypercoagulability and concomitantly enhanced fibrinolysis. Over the past decade, novel techniques for quantifying hemostasis have been introduced, which may provide new insights into this process. This review summarizes recent literature on the effect of extreme exertion of both short and long duration on coagulation, fibrinolysis, and recovery of hemostatic balance. Extreme exertion introduces a temporary hypercoagulable state, mainly through upregulation of the contact pathway by increased FVIII levels. Additionally, von Willebrand factor levels and platelet activation are increased. Simultaneously, increased fibrinolysis results from increased tissue-type plasminogen activator levels, suggesting a rebalanced hemostasis. The vascular endothelium appears to play a pivotal role in both processes. Data on the effect of exercise on endogenous anticoagulants are scarce. Hypercoagulability persists for hours to a day after prolonged extreme exertion, while fibrinolytic parameters appear to return to baseline levels more quickly. Hence, the balance in the rebalanced hemostatic state may be lost during recovery. Training induces lower amplitude of the hypercoagulable response, and quicker recuperation toward baseline. Repetitive exercise exhausts the endothelium, attenuating procoagulant changes. Additional research is needed to identify if the hemostatic balance is lost during recovery, and if so, when the shift toward thrombosis appears. Moreover, differences between sexes need to be addressed, since women are known to have a different pathophysiological mechanism behind cardiovascular events, but are underrepresented in recent literature.

Correlation between maternal and umbilical cord blood in pregnant women of Pokhara Valley: a cross sectional study

BackgroundComplete blood count is one of the routinely advised blood investigation during pregnancy. It is also utilized as a diagnostic tool for neonatal anemia, sepsis and determining hemostatic status of the newborn. The present study aims at estimating the complete blood count of maternal and umbilical cord blood at the time of delivery and to establish its correlation.MethodThis cross sectional study included 114 mothers and their healthy neonates born through normal vaginal delivery. Complete blood count of umbilical cord blood and maternal blood was estimated using automatic hematology analyzer.ResultsThe mean maternal and neonatal hemoglobin concentration was 11.14 ± 1.39 g/dL and 16.34 ± 2.01 g/dL respectively. A significant positive correlation was found between maternal and fetal hemoglobin concentration (p < 0.001 and Pearson R = 0.496). The correlation between maternal and fetal WBC, RBC and Platelet count was not statistically significant. A significant positive correlation was found between maternal and fetal MCV and MCH while PCV showed a non-significant positive correlation.ConclusionThere was moderately positive correlation between maternal and fetal hemoglobin, MCV and MCH. The cord blood hemoglobin was lower in babies born to anemic mothers. The decrease in hemoglobin followed the severity of anemia, however, the correlation did not exist in anemic mothers. It suggested that fetal hematological parameters are not reflective of maternal hemogram.

Platelet-leucocyte aggregation is augmented in cirrhosis and further increased by platelet transfusion.

Thrombocytopenia and circulating dysfunctional immune cells are commonly observed in patients with cirrhosis. Platelets may form complexes with neutrophils, monocytes and T cells modulating their function. We recently reported increased frequencies of platelet-complexed neutrophils in cirrhosis with evidence of neutrophil activation upon contact with healthy platelets in vitro. Whether this occurs in vivo following platelet transfusion and contributes to systemic inflammation and endothelial activation is unknown. To characterise platelet-leucocyte aggregation in cirrhosis and to determine whether elective platelet transfusion results in perturbations associated with changes in markers of haemostasis, inflammation or endothelial activation. We collected blood from cirrhotics (n = 19) before and following elective platelet transfusion. We measured platelet-leucocyte aggregation, activation and function, and markers of platelet activation, systemic inflammation and endothelial activation by flow cytometry. Haemostasis was assessed by thromboelastometry and plasma haemostatic proteins. We observed a 2.5-fold increase in platelet-complexed neutrophils in patients with cirrhosis compared with healthy subjects and twofold more platelets attached per monocyte and T cell. All platelet-complexed leucocytes expressed higher levels of activation markers and platelet-complexed neutrophils had higher resting oxidative burst and phagocytic capacity than their nonplatelet-complexed counterparts (P < 0.001); most pronounced in patients with cirrhosis. Paradoxically, platelet-complexed leucocyte frequency decreased with increasing MELD score. Platelet transfusion increased soluble CD40 ligand (platelet activation marker), the frequency of platelet-complexed monocytes (P < 0.05) and improved haemostatic status. Cirrhotic patients have activated circulating platelet-complexed leucocytes with increased platelet-monocyte aggregation following elective platelet transfusion. Elective platelet transfusion might therefore exacerbate immune dysfunction in cirrhosis.

THROMBOELASTOGRAPHY IN THE HEALTHY ASIAN ELEPHANT ( ELEPHAS MAXIMUS): REFERENCE INTERVALS AND EFFECTS OF STORAGE.

Hemorrhagic disease associated with elephant endotheliotropic herpesvirus infection is the most-frequent cause of mortality in captive Asian elephants ( Elephas maximus). Survival relies on intensive monitoring of hemostatic status. Thromboelastography (TEG) utilizes whole blood samples containing all the blood components of hemostasis and is therefore a sensitive indicator of the clinical status in the patient. This study was performed to assess the practicability of TEG in Asian elephants in a zoo environment. Citrated stabilized whole blood samples were obtained from 44 healthy Asian elephants. Kaolin-activated TEG was performed on whole blood at 60 min and 24 hr postsampling (to replicate shipment to an external laboratory) as well as on freeze-thawed plasma samples, 12-14 mo postsampling. Reference intervals were calculated for fresh whole blood and freeze-thawed plasma samples. In the 24-hr analysis, storage artifacts, likely due to cellular degeneration, resulted in a hypercoagulable thromboelastogram and thus reduced sensitivity for detecting coagulopathies. Therefore, delayed analysis of whole blood samples is not recommended.

Balanced haemostasis with both hypo- and hyper-coagulable features in critically ill patients with acute-on-chronic-liver failure

BackgroundCirrhotic patients have complex haemostatic abnormalities. Current evidence suggests stable cirrhotic (SC) patients have a “re-balanced” haemostatic state. However, limited data exists in acute decompensated (AD) or acute on chronic liver failure (ACLF) patients. MethodsWe utilised thrombin generation analysis, fibrinolysis assessment, and evaluation of haemostatic parameters to assess haemostasis in liver disease of progressive severity. ResultsThe study cohorts were comprised of: SC, n=8; AD n=44; ACLF, n=17; and Healthy Control (HC), n=35. There was a progressive increase across the cohorts in INR (p=0.0001), Factor VIII (p=0.0001) and VWF levels (p=0.0001) and a correspondingly decrease in anti-thrombin (p=0.0001), ADAMTS-13 (p=0.01) and fibrinogen levels (p=0.0001). In the presence of thrombomodulin, thrombin generation was equivalent or significantly higher in all the cohorts compared to HC (p=0.0001). Compared to AD, ACLF had a lower ETP (p=0.002) and thrombin peak (p=0.0001). There was no significant difference across the cohorts in clot lysis time (p=0.07), although compared to HC, AD had a significantly shorter lysis time (p=0.001). ConclusionsOur cohorts, despite significant differences in haemostatic parameters, displayed intact thrombin generation but progressive hypo-functional clot stability and potentially but not universal hyper-functional haemostasis.

Evaluation of Hemostatic Function with Thromboelastography in Dogs with Hypercoagulable Diseases

Thromboembolic complications are increasing in veterinary medicine. Thromboelastography (TEG) is a more comprehensive method for assessing the clotting process than standard plasma-based coagulation tests. This study compared the ability of TEG and standard coagulation tests to analyze the overall hemostatic state of dogs. The study involved 40 dogs with underlying diseases that predispose to hypercoagulability, including neoplasia, hyperadrenocorticism, immune-mediated diseases, gastrointestinal diseases, and protein-losing nephropathies and enteropathies, and 20 healthy dogs. Their overall hemostatic functional state was evaluated by TEG and routine coagulation assays, including activated partial thromboplastin time, prothrombin time, platelet count, and D-dimer concentration. TEG analysis showed significant differences in clot formation time, α angle, and maximum amplitude (MA) between diseased and control dogs (P ＜ 0.001 each). Increased MA was the most frequent abnormality on TEG and was indicative of hypercoagulability. TEG was useful in detecting hemostatic dysfunction in dogs with diseases associated with hypercoagulability. Dogs with TEG tracings indicative of hypercoagulability are likely to be in procoagulant states. Future prospective studies are needed to evaluate whether TEG tracings indicative of hypercoagulability are predictive of thrombosis in dogs.