Overall Coagulation Potential Research Articles

Acute effects of high intensity interval training versus moderate intensity continuous training on haemostasis in patients with coronary artery disease

Exercise training is associated with an acute net increase in coagulation, which may increase the risk of atherothrombosis in coronary artery disease (CAD) patients. We sought to compare the acute haemostatic effects of a bout of moderate-intensity continuous (MICT) and high-intensity interval training (HIIT) in patients with CAD. Patients after a recent myocardial infarction were randomized into a HIIT or MICT session of exercise training on a stationary bike. Blood was sampled at baseline, after the exercise bout and after a one-hour resting period. We measured overall haemostatic potential (OHP), overall coagulation potential (OCP), fibrinogen, D-dimer and von Willebrand factor (vWF) and calculated overall fibrinolytic potential (OFP). Linear mixed models for repeated measures were constructed to assess the treatment effect. A total of 117 patients were included. OCP, OHP, fibrinogen, D-dimer and vWF significantly increased after exercise and returned to baseline after a one-hour rest, OFP decreased after exercise and returned to baseline levels after a one-hour rest. Linear mixed models showed a significant difference between HIIT and MICT in fibrinogen (p 0.043) and D-dimer (p 0.042). Our study has shown that an exercise bout is associated with a transient procoagulant state in patients with CAD, with similar exercise-induced haemostatic changes for HIIT and MICT.

Overall Hemostatic Potential Assay Detects Risk of Progression to Post-Thrombotic Syndrome in Anticoagulated Patients following Deep Vein Thrombosis.

Deep vein thrombosis (DVT) frequently leads to post-thrombotic syndrome (PTS) which is challenging to predict and prevent. Identifying those at high risk of developing PTS may help to focus preventative strategies. Adults were recruited within 3 months of DVT diagnosis. Blood was sampled during the therapeutic anticoagulation phase. Overall hemostatic potential (OHP) assay, a spectrophotometric assay, was performed on platelet-poor plasma (PPP). In this assay, fibrin formation is triggered by small amounts of thrombin and termed the overall coagulation potential (OCP). Simultaneously, thrombin and tissue plasminogen activator are added to PPP and the resulting fibrin aggregation curve is the overall hemostatic potential (OHP). Fibrinolysis is expressed by the parameter overall fibrinolytic potential (OFP%). Patients were followed up at regular intervals. PTS was diagnosed if the Villalta score was ≥5 at least 3 months after the DVT diagnosis. Results were obtained from 190 patients (53.7% male, mean age 56.9 years). PTS developed in 62 (32.6%) patients. Patients with PTS displayed significantly higher median OCP (45.8 vs. 38.8 units, p = 0.010), OHP (12.8 vs. 9.2 units, p = 0.005) and significantly lower OFP (74.1 vs. 75.6%, p = 0.050). PTS patients had higher neutrophil/lymphocyte ratios (NLR) (2.3 vs. 1.9, p = 0.007). After multivariate analysis, proximal DVT location, history of varicose veins, NLR ≥ 2.6, OHP > 13.0 units and weight >108 kg were independent predictors for PTS. The c-statistic of the multivariate model was 0.77. This pilot study suggests that OHP testing while patients are still anticoagulated may assist in the prediction of PTS development and could assist in prognostication and targeting of preventative measures. However, larger prospective studies are needed to confirm these findings.

The Correlation between the Triglyceride-Glucose Index and Coagulation Markers in Patients with Recent Acute Myocardial Infarction.

Background Metabolic abnormalities and hypercoagulability seem to have an important predictive role in patients with coronary artery disease (CAD). The triglyceride-glucose (TyG) index has emerged as a good marker for metabolic syndrome with predictive value for cardiovascular events. Overall haemostatic potential (OHP) is a reliable global haemostatic essay to identify hypercoagulability in CAD patients. The aim of our study was therefore to evaluate a possible correlation between the TyG index and haemostatic derangements in patients with CAD. Methods Consecutive patients referred for the first follow-up visit after acute myocardial infarction between December 1, 2018, and March 31, 2020, and did not meet exclusion criteria were included. We determined OHP, overall coagulation potential (OCP), overall fibrinolytic potential (OFP), fibrinogen, D-dimer, and von Willebrand factor from peripheral blood samples. The TyG index was calculated with the previously described and validated formula. Linear regression models were constructed for the multivariate analysis. Results A total of 117 patients (mean age 56 ± 10 years, 20% women) were included. A correlation was found between TyG index and OCP (r = 0.229, p = 0.026), TyG index and OHP (r = 0.202, p = 0.050), and TyG index and fibrinogen (r = 0.271, p = 0.005). In the multivariate model which accounted for sex, age, and BMI, the correlation between TyG index and OCP (R2 0.108; ANOVA for regression p = 0.035; beta 2.08 [0.79-4.01], p = 0.042) and between TyG index and fibrinogen (R2 0.11; ANOVA for regression p = 0.015; beta 0.35 [0.08-0.62], p = 0.012) emerged as statistically significant. Conclusion The TyG index, a marker of metabolic syndrome, has a strong correlation with a hypercoagulability state in CAD, as determined by the OCP and higher fibrinogen levels. Our findings suggest that metabolic syndrome may be an important driver of atherothrombotic risk in patients with CAD.

Increased Expression of Extracellular Vesicles Is Associated With the Procoagulant State in Patients With Established Rheumatoid Arthritis.

This study sought to identify different subpopulations of extracellular vesicles (EVs) in plasma from female patients with established rheumatoid arthritis (RA) in relation to the activation of coagulation and fibrin formation in these patients. Forty women were included in the study, 20 patients and 20 age-matched healthy controls. The mean disease duration in patients was 13.0 (5.0–25.0) years, with medium to high disease activity despite ongoing treatment with low-dose prednisolone and methotrexate. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. The concentration of phosphatidylserine-positive (PS+) EVs; platelet (CD42a+), leucocyte (CD45+), monocyte (CD14+), and endothelial (CD144+)-derived EVs; and EVs-expressing tissue factor (CD142+), P-selectin (CD62P+), and E-selectin (CD62E+) were determined by flow cytometry analysis. Overall hemostasis potential (OHP) was assessed to follow the hemostatic disturbances, including the parameters for overall coagulation potential (OCP) and overall fibrinolytic potential (OFP). Fibrin clot turbidity was measured together with clot lysis time, and scanning electron microscopy was performed. Increased concentrations of PS+, CD42a+, CD142+, CD45+, CD14+, and CD62P+ EVs were found in plasma from patients with RA compared to healthy controls, and the concentrations of PS+, CD42a+, CD14+, and CD62P+ EVs were positively correlated with the inflammatory parameters in RA patients. Positive correlations were also found between the levels of PS+ and CD42a+ EVs and OCP as well as between the levels of PS+, CD42a+, and CD62P+EVs and OHP. The levels of PS+, CD42a+, CD14+, CD62P+, and CD62E+ EVs were negatively correlated with OFP. Elevated levels of circulating EVs of different cell origins were found in patients with established RA, in relation to the inflammatory burden and coagulation activation in the disease.

Utility of Global Coagulation Assays in Myeloproliferative Neoplasm: Thromboelastography, Thrombin Generation and Overall Haemostatic Potential

IntroductionMyeloproliferative neoplasm (MPN), such as polycythaemia vera (PV) and essential thrombocythaemia (ET), are independent risk factors for arterial and venous thrombotic events, with the estimated risks of thrombotic complications at diagnosis to be approximately 7-26% in ET patients and 19-32% in PV patients. As such, one of the management goals for MPN is directed towards modifying thrombosis risk via cytoreduction and anti-platelet therapies. However, there are no routinely available laboratory tests to evaluate the patient's thrombotic risk beyond the assessment of blood counts. Global coagulation assays such as thromboelastography, thrombin and fibrin generation may be better surrogate measures of thrombosis. This pilot study evaluates a cohort of MPN patients on current treatment, to further elucidate the impact of their prothrombotic milieu on global coagulation assays.MethodsParticipants with MPN (proven on bone marrow biopsy and/or molecular diagnosis) were recruited. Thromboelastography (using TEG® 5000) was performed on citrated whole blood while additional citrated blood samples were double spun at -2500G to obtain platelet-poor plasma (PPP) and stored in at -80°C within 2 hours of sample collection. The stored PPP were then used for thrombin generation assessment using the calibrated automated thrombogram (CAT), fibrinolysis evaluation using overall haemostatic potential assay (OHP) as well as p-selectin testing. The results were compared to our previously collected age-matched healthy normal controls (n=41).ResultsThirty-eight MPN patients (20 females, 18 males) with median age 65 years (range: 29-84) were recruited. There were 26 patients with ET (68.4%) including a patient with post-ET myelofibrosis, 8 patients with PV (20.5%), 3 patients with primary myelofibrosis and one with MPN, unclassifiable. The majority of the patients are JAK2 V617F positive (30/38, 79%). The haemoglobin level was comparable between both groups (p=0.73) although the MPN group had significantly increased platelet count (526 vs 237 x 109/L, p<0.01).When compared to normal controls, the thromboelastography parameters were mostly comparable including no significant difference in maximum amplitude or clot strength (59.6 vs 60.1 mm, p=0.42) although the clot lysis time (LY30) was significantly higher (5.1% vs 0.9%, p<0.01) in the MPN group, independent of the use of aspirin. Higher LY30 (>5%) was associated with higher haemoglobin (150.3 vs 138.4 g/L, p=0.03) but not platelet count. CAT parameters, however, showed higher thrombin peak (260.8 vs 227.3 nM; p=0.01) and velocity index (93.4 vs 70.1 nM.min; p<0.01) compared to the normal controls, but interestingly no difference in endogenous thrombin potential (1397.5 vs 1363.0 nM.min, p=0.52).Fibrin generation parameters, namely the overall coagulation potential (OCP) and OHP were significantly reduced in the MPN cohort (OCP - 56.5 vs 66.7, p<0.001; OHP - 27.4 vs 33.0, p<0.001) with preserved overall fibrinolytic potential (p=0.66). P-selectin was markedly increased in MPN patients compared to the normal controls (116.3 vs 54.6 ng/mL, p<0.001), with higher P-selectin levels correlating with a higher platelet counts (p<0.01).ConclusionThis study demonstrates that global coagulation assays can provide additional information regarding the thrombotic risks in MPN patients. The MPN patients in our study had significantly higher lysis time and a reduction in fibrin generation parameters, which is contradictory to the prothrombotic nature of MPN. It may be a protective prognostic marker in the setting of treatment and could represent an underlying compensatory effect. Despite being a treated MPN cohort, the P-selectin remained higher in these patients and correlated with higher platelet count, suggesting that the higher P-selectin seen is likely of platelet subtype, though this did not correlate with changes in other global coagulation assay parameters despite thrombin being a known trigger of P-selectin exocytosis. Further prospective clinical studies including assessment of fibrinolysis markers and markers of platelet and endothelial function to evaluate and confirm these findings are proposed. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

P.849A five-year follow up study of a naturalistic cohort treated with long-acting injectable antipsychotics

Patients with schizophrenia are at increased risk of venous thromboembolism. The mechanisms underlying this association are poorly understood.We investigated whether there is a global hypercoagulable state in patients with schizophrenia utilising the overall haemostatic potential (OHP) assay which assesses overall coagulation potential (OCP), haemostatic potential (OHP) and fibrinolytic potential (OFP).Citrated plasma was collected for OHP assays from patients with schizophrenia on long-term antipsychotic treatment and compared with healthy age- and sex-matched controls. Time courses of fibrin formation and degradation were measured by spectrophotometry (absorption of 405 nm) after the addition of tissue factor and tissue plasminogen activator to plasma.Ninety patients with schizophrenia (antipsychotic treatment-15.9 ± 9.7 years) and 30 controls were recruited. Patients with schizophrenia had higher rates of smoking and levels of inflammatory markers (high-sensitivity C-reactive protein and neutrophil-to-lymphocyte ratio) than controls. Whilst D-dimer, fibrinogen and platelet count did not differ between patients with schizophrenia and controls, the OCP (54.0 ± 12.6 vs 45.9 ± 9.1, p = 0.002) and OHP (12.6 ± 5.8 vs 7.2 ± 3.7, p < 0.001) were higher, and OFP was lower (76.6 ± 9.8% vs 84.9 ± 6.4%, p < 0.001) in patients with schizophrenia, implying both a hypercoagulable and hypofibrinolytic state in these patients. Importantly, abnormalities in overall coagulation were independently predicted by levels of plasminogen-activator-inhibitor-1, fibrinogen, platelet count, inflammatory markers and plasma triglycerides, suggesting a multifactorial aetiology.Patients with schizophrenia have evidence of a global hypercoagulable and hypofibrinolytic state which may contribute to their increased risk of venous thromboembolism.

Venous thromboembolism in anti-neutrophil cytoplasmic antibody-associated vasculitis: an underlying prothrombotic condition?

ObjectivesWe investigated the incidence and potential underlying risk factors of venous thromboembolism (VTE) in patients with AAV. We assessed haemostatic disturbances and factors that might contribute to the risk of development of VTE.MethodsANCA-positive AAV patients (n = 187) were included. Previously identified risk factors for VTE and current medication were retrieved from the medical records. We assessed haemostasis using different methods [endogenous thrombin potential (ETP), overall haemostatic potential (OHP), overall coagulation potential (OCP) and overall fibrinolysis potential (OFP)] in patients with active AAV (n = 19), inactive AAV (n = 15) and healthy controls (n = 15).ResultsTwenty-eight VTEs occurred in 24 patients over a total follow-up time of 1020 person-years. A majority of VTEs occurred within the first year after diagnosis. Old age (P < 0.01), ongoing prednisolone treatment and recent rituximab administration were more common in the VTE group (P < 0.05 for all). ETP and OHP were significantly increased and OFP significantly decreased in plasma from active compared with inactive AAV patients (P < 0.05, P < 0.01 and P < 0.05, respectively) and healthy controls (P < 0.001). We could not confirm previously reported risk factors for VTE development.ConclusionA high prevalence of VTE in AAV patients was seen within the first year after diagnosis, suggesting that disease activity contributes to development of VTE. Old age and concurrent treatment should also be taken into account when estimating VTE risk. The results also indicate disturbances in the haemostatic balance towards pro-thrombotic conditions in AAV patients, where ETP and OHP might be useful markers for identifying patients at high risk.

Assessment of hemostatic disturbances in women with established rheumatoid arthritis

ObjectivesThis study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity.MethodNinety women were included in the study, 42 patients and 48 age-matched healthy controls. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. Two global hemostatic assays were employed, namely endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). The parameters of the ETP assay (ETP, C-max, t-lag, t-max) and OHP assay (overall coagulation potential (OCP) and overall fibrinolytic potential (OFP)) were assessed. Moreover, the parameters of the fibrin clot (lag time, Max Abs, and slope) were measured by clot turbidity and scanning electron microscopy (SEM). Both patients and controls were divided into four subgroups according to menopause status.ResultsThe premenopausal controls differed significantly from all other subgroups in terms of diminished levels of ETP (p = 0.02), C-max (p = 0.01), OCP (p = 0.02), OHP (p = 0.001), and Max Abs (p = 0.008), while OFP (p = 0.0001) was increased. This tendency was not seen in the premenopausal RA patients compared with the postmenopausal RA patients. SEM images showed denser clots composed of thinner fibers in samples from RA patients. The disease activity measured by DAS28 correlated with OCP and OHP (r = 0.54; p = 0.001 and r = 0.44; p = 0.003, respectively) indicating persistent hypercoagulable condition in the whole group of RA patients.ConclusionsOur results point towards coagulation activation in premenopausal women with established RA. The patients were well characterized, which enabled assessment in a real-life setting.Key Points• Extensive assessment points towards persistent coagulation activation in premenopausal women with established rheumatoid arthritis.• Impaired thrombin generation and fibrin formation are associated with menopause in healthy women, while rheumatoid arthritis closes the gap within patients regarding menopause.• Fibrin morphology is unfavorably altered and fibrinolysis is decreased in patients with established rheumatoid arthritis.• Increased activity of thrombin activatable fibrinolysis inhibitor (TAFI) may contribute to impaired fibrinolysis in patients with rheumatoid arthritis.

Increased Coagulation and Decreased Fibrinolysis as Measured with Overall Hemostatic Potential Are Dependent on BMI and Not Associated with PCOS.

Overall hemostatic potential (OHP) captures all factors that affect coagulation and fibrinolysis cascade. It has not yet been assessed in polycystic ovary syndrome (PCOS). The aim of the study was to identify the relationship of OHP with a syndrome per se and body mass index (BMI). In 90 women with PCOS aged 30.9 ± 8.1 years (50 obese, 13 overweight, and 27 lean) and 21 healthy age-matched controls (11 obese and 10 lean), OHP with overall coagulation potential (OCP) and overall fibrinolytic potential (OFP) was determined spectrophotometrically. OFP was calculated. OHP increased with BMI in PCOS (9.6 ± 2.3 in lean, 12.5 ± 5.1 in overweight, and 15.5 ± 3.8 Abs-sum in obese) and in controls (9.1 ± 1.0 in lean and 17.3 ± 4.6 Abs-sum in obese). There was significant difference between lean and obese PCOS (P < 0.001) and between lean and obese controls (P < 0.001). OCP also increased with BMI in PCOS (P < 0.001 for lean vs. obese) and in controls (P < 0.001 for lean vs. obese). OFP decreased with BMI in PCOS (P < 0.001 for obese vs. overweight vs. lean) and in controls (P < 0.001 for obese vs. lean). OHP in healthy obese and obese PCOS did not differ significantly, while OHP for healthy obese was increased in comparison to overweight and lean PCOS (P < 0.001). PCOS was not associated with increased OHP compared with BMI and age-matched controls. However, increase in OHP was positively associated with BMI in PCOS and healthy women.

Persistent global hypercoagulability in long-term survivors of acute pulmonary embolism.

Hypercoagulable and/or hypofibrinolytic states are risk factors for venous thromboembolism (VTE) including acute pulmonary embolism. Current screening for thrombophilia is targeted towards identifying a specific defect and guidelines recommend a population-based rather than individualized strategy for anticoagulation treatment. We investigated whether there is a global hypercoagulable state in long-term survivors of pulmonary embolism no longer receiving therapeutic anticoagulation utilizing the overall haemostatic potential (OHP) assay, which assesses overall coagulation potential (OCP), OHP and overall fibrinolytic potential (OFP). Long-term survivors of acute pulmonary embolism were identified from a local registry and OHP assays were performed and compared with age and sex-matched controls without pulmonary embolism. Time courses of fibrin formation and degradation were measured by spectrophotometry (absorption 405 nm) after addition of tissue factor and tissue plasminogen activator to plasma. OHP assays were performed in 67 long-term survivors of single pulmonary embolism (7.9 ± 1.4 years after pulmonary embolism) and 20 age (61.7 ± 11.2 vs 56.6 ± 6.4 years, P = 0.06) and sex (P = 0.45)-matched controls. Survivors of pulmonary embolism were more hypercoagulable as reflected by significantly higher OCP (56.4 ± 13.0 vs 49.9 ± 6.9, P = 0.03) and had impaired fibrinolysis with higher OHP (12.6 ± 7.0 vs 5.9 ± 2.0, P < 0.001) and lower OFP (78.1 ± 9.4 vs 88.2 ± 2.9, P < 0.001) compared with controls. Importantly, these abnormalities in overall coagulation were independently predicted by levels of fibrinogen, platelet count, shortened activated partial thromboplastin time and inflammatory markers suggesting a multifactorial cause. Long-term survivors of pulmonary embolism demonstrate enhanced global coagulation and reduced fibrinolytic potential. Assessment of global coagulation may provide new insights into the aggregate effects of multiple prothombotic factors and long-term risk of VTE recurrence.

Global hypercoagulability in patients with schizophrenia receiving long-term antipsychotic therapy

BackgroundPatients with schizophrenia are at increased risk of venous thromboembolism. The mechanisms underlying this association are poorly understood. AimsWe investigated whether there is a global hypercoagulable state in patients with schizophrenia utilising the overall haemostatic potential (OHP) assay which assesses overall coagulation potential (OCP), haemostatic potential (OHP) and fibrinolytic potential (OFP). MethodCitrated plasma was collected for OHP assays from patients with schizophrenia on long-term antipsychotic treatment and compared with healthy age- and sex-matched controls. Time courses of fibrin formation and degradation were measured by spectrophotometry (absorption of 405nm) after the addition of tissue factor and tissue plasminogen activator to plasma. ResultsNinety patients with schizophrenia (antipsychotic treatment-15.9±9.7years) and 30 controls were recruited. Patients with schizophrenia had higher rates of smoking and levels of inflammatory markers (high-sensitivity C-reactive protein and neutrophil-to-lymphocyte ratio) than controls. Whilst D-dimer, fibrinogen and platelet count did not differ between patients with schizophrenia and controls, the OCP (54.0±12.6 vs 45.9±9.1, p=0.002) and OHP (12.6±5.8 vs 7.2±3.7, p<0.001) were higher, and OFP was lower (76.6±9.8% vs 84.9±6.4%, p<0.001) in patients with schizophrenia, implying both a hypercoagulable and hypofibrinolytic state in these patients. Importantly, abnormalities in overall coagulation were independently predicted by levels of plasminogen-activator-inhibitor-1, fibrinogen, platelet count, inflammatory markers and plasma triglycerides, suggesting a multifactorial aetiology. ConclusionPatients with schizophrenia have evidence of a global hypercoagulable and hypofibrinolytic state which may contribute to their increased risk of venous thromboembolism.

Enhanced thrombin generation in women with a history of oral contraception-related venous thrombosis

In women who suffer venous thrombosis (VT) during oral contraceptive (OC) use, a transient risk factor (OC) is removed during the acute event, while most co-existing forms of thrombophilia persist and presumably continue to maintain hypercoagulability. The aim of this study was to establish if hypercoagulability persists long after OC-related VT and if it could be attributed to thrombophilia. 60 women (age 33.0 ± 8.5 years) were investigated 5 - 64 (median 33) months after OC-related VT (patients) and compared to 63 apparently healthy women (controls). All women were tested for thrombophilia, activated partial thromboplastin time (APTT), fibrinogen, D-dimer, P-selectin and C-reactive protein. Thrombin generation was measured by Technothrombin® TGA assay. Overall haemostasis potential (OHP) assay with overall coagulation potential (OCP) and overall fibrinolytic potential (OFP) as supplementary parameters were measured by repeated fibrin formation and degradation registration. In patients increased endogenous thrombin potential (4,205 ± 440 nM x min vs 4,015 ± 421 nM x min, p=0.017), increased OCP (22.6 ± 4.6 Abs-sum vs 20.8 ± 4.1 Abs-sum, p=0.025), shorter APTT (30.9 ± 3.8s vs 33.4 ± 3.6s, p<0.001) and lower antithrombin activity (99, 93-105% vs 104, 100-109%, p<0.05) were observed. Thrombophilia was observed in 22/60 (36%) patients and in 5/63 (7.9%, p<0.001) controls. The only significant difference between thrombophilic and non-thrombophilic patients was higher soluble P-selectin in the former subgroup (22, 20-33 μg/L vs 17, 12-22 μg/L, p=0.012). In women with a history of OC-related VT persistent hypercoagulability was observed, which, however was not augmented by the presence of thrombophilia.

C0239 Which are the most evidence-based and cost-effective strategies for treating patients with heart failure?

and potentially at greater risk of developing early restenosis/ reocclusion after femoropopliteal percutaneous transluminal angioplasty (PTA). Methods: In 44 patients with atherosclerotic peripheral artery disease undergoing PTA blood was obtained 1 day before (sample 1), during (samples 2, 3, 4 and 5) and 1 day after PTA (sample 6). Samples 3 and 5 were arterial, others were venous. Besides OHP, Overall Coagulation Potential (OCP) was determined in plasma after addition of thrombin only and Overall Fibrinolitic Potential (OFP) was calculated as [(OCP-OHP)/OCP]x100. In samples obtained during PTA unfractionated heparin applied during the procedure was neutralized with polybrene. One month after PTA restenosis was diagnosed in 10 patients in 17 patients treated artery remained patent, while other 17 will be examined in the following weeks. Results: In all 44 samples 1 and 6 OHP and OCP were significantly higher (pb0.001) compared to samples 2–5, while no difference was observed for OFP. OHP, OCP and OFP in samples 1 did not differ significantly from samples 6 and no difference was observed between arterial (3, 5) and venous (2, 4) blood samples. OHP, OCP and OFP of patients with restenosis did not differ significantly from patients without restenosis (Table).

Diurnal changes and levels of fibrin generation are not altered by continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA)

Obstructive sleep apnoea (OSA) is associated with increased cardiovascular disease (CVD) risk. In the general population, CVD events peak at 9:00-10:00 AM, associated with diurnal changes in thrombotic potential. However in OSA, these CVD events occur frequently at night. Measuring thrombotic potential across the sleep-wake cycle may provide insight into the temporal association of OSA with CVD. This study aimed to determine diurnal changes in fibrin generation in OSA and whether treatment of OSA with continuous positive airway pressure (CPAP) alters fibrin generation across the sleep-wake cycle. In a randomised placebo-controlled crossover trial, patients with OSA were assigned to two months each of therapeutic CPAP and placebo. After each treatment period, fibrin generation was determined by overall haemostatic potential assay at seven time points over 24 hours (h). Twenty-eight patients (25 men, 3 women) with severe OSA (Apnoea Hypopnoea Index = 37.9 ± 23.9/h, Oxygen Desaturation Index 31.3 ± 22.4/h) completed the study. All parameters, except lag time to fibrin generation, showed significant diurnal changes, both on CPAP and placebo. Compared to 9:00 AM, fibrin generation parameters were significantly lower at midnight and 3:00 AM for overall coagulation potential (OCP), overall haemostasis potential (OHP), maximum optical density, and maximum slope (all p≤0.001). CPAP produced no change in fibrin generation parameters compared to placebo. In severe OSA patients, fibrin generation peaked at 6:00 AM and 9:00 AM rather than during the sleep period (midnight and 3:00 AM). These findings suggest a prothrombotic shift in the morning similar to individuals without OSA. There was no difference between CPAP and placebo on fibrin generation.

Screening Haemostasis – Looking for Global Assays: The Overall Haemostasis Potential (OHP) Method – A Possible Tool for Laboratory Investigation of Global Haemostasis in Both Hypo- and Hypercoagulable Conditions

A broad spectrum of global haemostatic assays has recently been developed and modified in an attempt to overcome the drawbacks of classical screening tests used for evaluation of coagulation and fibrinolysis. The Overall Haemostasis Potential (OHP) assay is one of such assays. The assay is based on repeated spectrophotometric registration of fibrin-aggregation in citrated plasma, to which small amounts of exogenous thrombin, tissue type plasminogen activator and calcium chloride have been added. The area under the fibrin aggregation curve which then develops is calculated and is the laboratory parameter used for OHP determination. The Overall Coagulation Potential (OCP) and Overall Fibrinolytic Potential (OFP) are supplementary parameters of OHP, providing details of underlying changes in coagulation and/or fibrinolysis. The sensitivity of the assay for detecting hypercoagulation in normal pregnancy, in preeclampsia, some thrombophilias, coronary heart disease, diabetes, stroke and vascular surgery has been evaluated. Since the assay can monitor haemostasis balance in the sample, it may serve as a laboratory tool to determine hypocoagulation, especially in patients with haemophilia A or B. Preliminary findings also indicate that the OHP assay may be useful in the monitoring of anticoagulant treatments. Larger controlled clinical studies are, however, mandatory before a definite conclusion about the usefulness of the method can be drawn.

A Simple and Rapid Laboratory Method for Determination of Haemostasis Potential in Plasma: II. Modifications for Use in Routine Laboratories and Research Work

To offer a suitable method for use in routine laboratories and research work, some modifications were made in the assay of overall haemostatsis potential (OHP) we developed earlier. Thrombin in a decreased dose with or without tissue-type plasminogen activator was added to plasma for initiation of fibrinogen clotting. Areas under two fibrin-aggregation curves i.e., abovementioned OHP and overall coagulation potential (OCP) were thus created. A difference between the two parameters reflects the overall fibrinolysis potential (OFP), calculated by ((OCP−OHP)/OCP)×100%. To obtain reference ranges, investigations were performed in 142 healthy adults of different ages and in 29 healthy women with a normal pregnancy. In 16 patients suffering from coronary heart disease (CHD), OCPs and OHPs increased but OFPs decreased. In 10 pre-eclamptic women with moderate enhancement of OCP, the OHPs became noticeably higher in most while the OFPs lower. Extremely low or undetectable levels of OHP and OCP were shown in samples of Factors VIII-, IX-, VII-, V-, X- or II-deficient plasma. In 13 healthy volunteers treated with acetylsalicylic acid (ASA), OHPs expectedly declined during the administration and rose again after withdrawal. The above findings demonstrate that the modifications in the present study have rendered the method more effective for detecting haemostatic changes and relevant for monitoring treatments.