Prothrombotic Changes Research Articles

Metabolic status in normal-weight and obese young individuals

Abstract Funding Acknowledgements Type of funding sources: None. Introduction. The concept of metabolic health in obese and normal-weight individuals remains controversial. It is important to study cardiometabolic risk factors in various phenotypes of normal-weigth and overweight/obese young individuals, which may be a practical and important step towards personalised medicine. Purpose. To estimate associations of cardiometabolic risk factors with adipokines in normal weight, overweight/obese young individuals. Methods. Study design: cross-sectional study. The study included 251 patients. All patients were divided into 4 groups: group I - metabolically healthy individuals with normal-weight aged 24.5 [22-31] years (n = 62); group II - metabolically unhealthy individuals with normal-weight aged 28 [23-38] years (n = 57); group III - metabolically healthy overweight/obesity aged 30 [24-36] years (n = 16); group IV - metabolically unhealthy overweight/obesity aged 36 [28.5-41] years (n = 116). We perfomed clinical examination, measured lipids, serum concentrations of glucose, insulin, leptin, adipokines, fibrinogen, type I plasminogen activator inhibitor (PAI-1). Data analysis was performed using the statistical package MedCalc Saftware (Version 19.6). p < 0.05 were taken as statistically significant. Results. The highest concentrations of glucose, insulin and the insulin resistance index HOMA-IR were found in groups with a metabolically unhealthy profile (group II and IV) compared to group I and III. The highest concentrations of triglycerides, LDL, fibrinogen and PAI-1, as well as the lowest values of HDL, were found in group IV vs group I, II, III. The concentration of leptin was higher in metabolically unhealthy overweigt/obesity individuals, as well as lower concentration of adiponectin in group III and IV compared to group I and II. In young individuals with a metabolically healthy phenotype, we obtained positive linear correlations between PAI-1 and systolic (r = 0.337, p = 0.04) and diastolic blood pressure (r = 0.314, p = 0.022), as well as negative associations between waist circumference and HDL (r= - 0.374, p = 0.003). In young individuals with a metabolically unhealthy phenotype, the most significant positive linear correlations were found between the concentrations of leptin and fibrinogen (r = 0.490, p = 0.003), as well as systolic blood pressure and HDL (r = 0.307, p = 0.02). In the group of young adults with metabolically healthy obesity the only negative correlation between waist circumference and HDL cholesterol (r= - 0,599, p = 0,031) was revealed. The most significant correlations among metabolically unhealthy obese individuals were obtained between diastolic blood pressure and fibrinogen (r = 0.346, p < 0.001), as well as body mass index and leptin (r = 0.521, p < 0.001). Conclusion. The most pronounced disorders of carbohydrate and lipid metabolism in combination with an imbalance of adipokines and prothrombotic changes in hemostasis were found in young individuals with metabolically unhealthy owerweight/obesity.

Venous thrombosis with oral postmenopausal hormone therapy: Roles of activated protein C resistance and tissue factor pathway inhibitor

BackgroundOral postmenopausal hormone therapy (HT) increases the risk of venous thrombosis (VT). We postulated that activated protein C (APC) resistance induced by HT is one of the mechanisms causing VT, and also assessed the role of one of the main determinants of APC resistance (i.e., tissue factor pathway inhibitor [TFPI]). MethodsWe performed a nested case‐control study embedded within two Women's Health Initiative hormone trials. Women were randomized to hormone therapy or placebo. Biomarkers were measured at baseline and after 1 year in 217 cases and 817 controls. ResultsIncreased APC resistance and decreased TFPI at baseline were associated with VT (odds ratio 1.20–2.06). However, women with such prothrombotic profile at baseline did not have further increased risk of VT when randomized to HT compared with placebo. Although there was no change in APC resistance or TFPI in placebo group after 1 year, HT group showed prothrombotic changes in the biomarkers (i.e., an increase in APC resistance) (mean [standard deviation] 0.39 [0.54]) and decrease in TFPI (−0.21 [0.50]: free TFPI, −0.24 [0.22]: TFPI activity −0.22 [0.20]: total TFPI). However, HT induced prothrombotic change in biomarkers did not increase risk of VT. ConclusionWomen with prothrombotic levels of APC resistance and TFPI at baseline were not at increased risk of VT when randomized to HT compared with placebo. This suggests that testing for these biomarkers before starting HT is not required. HT led to prothrombotic change in these biomarkers after one year, but this did not relate to increased risk of VT.

Analysis of D-Dimer Levels among Covid -19 Positive Patients in a Tertiary Care Hospital in Bangalore

Introduction: Pro-thrombotic changes are stimulated by Corona Virus as it has an affinity forendothelium and lung structures and this may explain its association with thrombotic events,reduction of pulmonary gas exchange, respiratory distress, and death. D-dimer is a specific markerof the breakdown of a fibrin clot and has been used as a diagnostic and prognostic marker in VTEand other coagulation disorders. Objectives: The objective of this study was to assess thecorrelation of the D-Dimer levels and disease severity among COVID-19 patients. Materials andmethods: This is a retrospective study done over 6 months from July 2020 to December 2020 in atertiary care hospital in Bangalore. All the COVID- 19 positive cases who were admitted to ourhospital were audited regarding the D-dimer levels during admission and the course of thetreatment. Results: Coagulation disorder occurred at the early stage of COVID-19 infection, with1066 (57.7%) patients having increased D-dimer levels. Out of 1846 COVID 19 patients 106(5.7%)patients died due to complications. 106 patients who deceased, all the patients had anincreased D dimer value either in the first lab test or in the consecutive tests. Among 106 patients56(52.8%) patients had increased D-dimer at the first lab test, 32 (30.1%) had D-dimer increasedat the second and 18(16.98%) in third lab tests. The increased D-dimer levels were closelyassociated with the progression of the disease and also the changes in the CT imaging. Conclusion:The increase in D-Dimer levels also increased the complications in the COVID-19 patient. So it isnecessary to continuously monitor D-dimer levels and labelled anticoagulation as management toolsfor COVID-19 disease to prevent complications and reduce interventions.

Effect of blood loss during caesarean section on coagulation parameters

IntroductionVenous thrombosis is the leading cause of pregnancy-related maternal morbidity and mortality. The thrombosis risk is increased by caesarean section and blood loss, though underlying mechanisms of these prothrombotic changes remain unknown. Materials and methodsThis prospective study recruited 50 pregnant women at term undergoing elective caesarean section at University Hospital Magdeburg, Germany. Blood loss during surgery was correlated with the changes in total protein S, full length TFPI (TFPIfl), prothrombin, the endogenous thrombin potential (ETP) and resistance to activated protein C (APCsr) determined via calibrated automated thrombography. ResultsMean blood loss was 506 ml (95%CI: 456 to 557 ml). Total protein S was 0.63 (95%CI: 0.60 to 0.67) U/ml preoperatively, decreased by 14.8% after caesarean section and almost normalised five days later. TFPIfl was 0.47 (95%CI: 0.41 to 0.53) U/ml before, remained unchanged immediately after and increased by 11.5% five days after surgery. Prothormbin was 1.10 (95%CI: 1.03 to 1.16) U/ml preoperatively, reduced by 10.4% immediately after and increased again five days after caesarean section, exceeding the preoperative values by 4.4% (−0.7 to 9.6). The ETP decreased by 3.9%, whereas the APCsr increased by 37.0% immediately after caesarean section. The changes in total protein S, prothrombin, thrombin generation and APC resistance showed a trend to be more pronounced in the subgroups with higher blood loss. DiscussionModerate blood loss during caesarean section hardly reduces thrombin generation but aggravates pregnancy-induced APC resistance and combined deficiency of TFPI and protein S, which can account for the increased thrombosis risk in early puerperium.

COVID-19-associated coagulopathy: review of current recommendations for diagnosis, treatment and prevention

The coronavirus infection COVID-19 is a highly contagious disease caused by the SARS-CoV-2 virus. Specific prothrombotic changes of the hemostasis system in COVID-19 are associated with increased incidence of venous thromboembolic complications. The article is a literature review on the diagnosis, treatment and prevention of coagulopathy and venous thromboembolic complications associated with COVID-19. 11 studies evaluating the frequency of registration of venous thromboembolic complications and 11 clinical recommendations on correction of coagulopathy published before May 22, 2020 have been studied. The frequency of venous thromboembolic complications was unexpectedly high: 8–13% in the general ward and 9–18% in the intensive care unit against the background of preventive measures. Preventive doses of anticoagulants, low-molecular weight heparins or unfractionated heparin are indicated to all hospitalized patients. Prolonged prophylaxis after discharge from hospital can be recommended for those at high risk of venous thromboembolic complications and low risk of bleeding. An increase in D-dimer may be considered as an indication for instrumental detection of venous thromboembolic complications. If there is a suspicion of venous thromboembolic complications, anticoagulant therapy at therapeutic doses can be started before the diagnosis is confirmed: during inpatient treatment preference should be given to low-molecular heparin or unfractionated heparin, after discharge from hospital it is recommended to transfer to direct oral anticoagulants for a period of at least 3 months. Routine prevention of venous thromboembolic complications in ambulatory patients is not recommended.

Prothrombotic changes in patients with COVID‐19 are associated with disease severity and mortality

Background and AimsPatients with severe coronavirus disease 2019 (COVID‐19) are at significant risk of thrombotic complications. However, their prothrombotic state is incompletely understood. Therefore, we measured in vivo activation markers of hemostasis, plasma levels of hemostatic proteins, and functional assays of coagulation and fibrinolysis in plasma from patients with COVID‐19 and determined their association with disease severity and 30‐day mortality. MethodsWe included 102 patients with COVID‐19 receiving various levels of respiratory support admitted to general wards, intermediate units, or intensive care units and collected plasma samples shortly after hospital admission. ResultsPatients with COVID‐19 with higher respiratory support had increased in vivo activation of coagulation and fibrinolysis, as reflected by higher plasma levels of d‐dimer, thrombin‐antithrombin, and plasmin‐antiplasmin complexes as compared to patients with no to minimal respiratory support and healthy controls. Moreover, the patients with COVID‐19 with higher respiratory support exhibited substantial ex vivo thrombin generation and lower ex vivo fibrinolytic capacity, despite higher doses of anticoagulant therapy compared to less severely ill patients. Fibrinogen, factor VIII, and von Willebrand factor levels increased, and ADAMTS13 levels decreased with increasing respiratory support in patients with COVID‐19. Low platelet count; low levels of prothrombin, antithrombin, and ADAMTS13; and high levels of von Willebrand factor were associated with short‐term mortality. ConclusionsSevere COVID‐19 is associated with prothrombotic changes with increased in vivo activation of coagulation and fibrinolysis, despite anticoagulant therapy.

Uremic serum induces prothrombotic changes in venous endothelial cells and inflammatory changes in aortic endothelial cells

Background Uremia induces various pathologic changes in the endothelium. However, there is limited information about the differences of these effects in endothelial cells originating from different parts of the vascular tree. Methods The effect of uremic serum obtained from patients with end stage renal failure on the gene expression and secretory activity of venous endothelial cells (VEC) and aortic endothelial cells (AEC) was studied in in vitro culture. Results In VEC, the expression of genes regulating the synthesis of von Willebrand factor (vWF) was increased by 254% (p<.005), vascular endothelial growth factor (VEGF) synthesis by 150% (p<.001), tissue plasminogen activator (t-PA) synthesis by 62% (p<.005), platelet endothelial cell adhesion molecule by 89% (p<.005), and the expression of gene regulating interleukin-6 (IL-6) synthesis was reduced. In AEC, the expression of the gene regulating synthesis of IL-6 was increased by 174% (p<.001), and the expression of the other genes was reduced. The secretion of IL-6 was reduced in VEC by 38% (p<.01) and increased in AEC by 55% (p<.005). In VEC, increased synthesis of VEGF 64% (p<.001) vWF (+34%, p<.01), and t-PA (+53%, p<.002) was observed, and in AEC it was reduced. Conclusions VEC and AEC respond in different ways after exposure to uremic serum. VEC acquires the prothrombotic phenotype, whereas in AEC the inflammatory phenotype appears.

COVID‐19–related prothrombotic changes increase with lung injury and remain unaffected by anticoagulation therapy

The coronavirus disease 2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) evokes an intricate global public health crisis. Scientists all over the world are trying to decipher the mechanisms by which SARS‐CoV‐2 induces a systemic response in severely affected individuals, which contributes to a high mortality rate. Hence, a clear understanding of the underlying pathology is warranted to allow for optimal treatment of patients, which—in the case of COVID‐19—seems diverse and complex.

Thrombosis of pulmonary vasculature despite anticoagulation and thrombolysis: The findings from seven autopsies

BackgroundVenous thromboembolism (VTE) with the prevalence of pulmonary microcirculatory thrombosis is considered a common complication of novel coronavirus disease (COVID-19) that develops despite anticoagulation. MethodsThe clinical course of the disease and the autopsy findings of seven deceased patients with verified COVID-19 were analyzed. The chest computed tomography (CT) scan was routinely performed while CT pulmonary angiography and a duplex ultrasound scan (DUS) of the lower limbs were used in cases of suspected VTE. The VTE prophylaxis was administered to all patients with intermediate or therapeutic doses of low-molecular-weight heparin. The histological examination of the lung tissue and other organs was performed with particular attention paid to the pulmonary vasculature. ResultsVenous thromboembolism, including deep vein thrombosis in one patient and pulmonary artery thrombosis in two patients, was confirmed by imaging tests despite anticoagulation. Systemic thrombolysis was performed in two patients with putative and confirmed pulmonary embolism. An autopsy revealed the signs of acute respiratory distress syndrome in all seven patients. Abnormalities of lung vessels were found in all cases and were represented by dystrophy and necrosis in the endothelium and muscle fibers, and by infiltration by plasmatic cells, neutrophils, and lymphocytes. Multiple clots of variable maturity were observed. All those changes developed despite anticoagulation and were preserved after systemic thrombolysis. ConclusionInflammatory and prothrombotic changes in the arterial wall in parallel with the lack of lung perfusion may cause diffuse arterial thrombosis in the lungs. This background may be responsible for the low response to systemic anticoagulation and thrombolysis in severe forms of COVID-19.

Maternal and paternal carriage of the annexin A5 M2 haplotype: a possible risk factor for recurrent implantation failure (RIF)

ObjectiveThis study was carried out to determine the potential role of the M2/ANXA5 haplotype as a risk factor for recurrent implantation failure (RIF). Carriage of the M2/ANXA5 haplotype that induces prothrombotic changes has been implicated in failure of early pregnancies and placenta-mediated complications (preeclampsia, IUGR, preterm birth).Material and methodsIn the present case control study, 63 couples (females and males) with RIF presenting for IVF/ICSI to the Fertility Center of [masked] were analyzed. RIF was defined as ≥ 4 consecutive failed ART-transfers of ≥ 4 blastocysts or ≥ 8 cleavage-stage embryos of optimal quality and maternal age ≤ 41. Fertile female controls (n = 90) were recruited from the same center. Population controls (n = 533) were drafted from the PopGen biobank, UKSH Kiel.ResultsCouples carrying the M2/ANXA5 haplotype turned out to have a significantly increased relative risk (RR) for RIF. Compared with female fertile controls, RR was 1.81 with p = 0.037 (OR 2.1, 95%CI 1.0–4.3) and RR was 1.70, with p = 0.004 (OR 2.0, 95%CI 1.2–3.1) compared with population controls (15.4% M2 carriers). Male partners were comparable with RIF females for M2/ANXA5 haplotypes (28.6% vs. 23.8%, p = 0.54). RIF females compared with population controls had a RR of 1.55 (p = 0.09) and RIF males compared with population controls had a RR of 1.9 (p = 0.01). Couples with ≥ 7 failed transfers showed a RR of 1.82 (p = 0.02) compared with population controls.ConclusionOur findings suggest that maternal as well as paternal M2/ANXA5 haplotype carriages are risk factors for RIF. These results allow new insights into the pathogenesis of RIF and might help to identify relevant risk groups.

The Effect of Obesity on the State of Platelet-plasma Hemostasis in Patients with Essential Hypertension in Combination with Non-alcoholic Fatty Liver Disease

Obesity, being one of the main modified risk factors for the development of pathology of the cardiovascular system, determines its rapid progression, more severe course and a high incidence of complications. With the prevalence of obesity, the incidence of hypertension (HT), non-alcoholic fatty liver disease (NAFLD), and, as a result, cardiovascular events increases.The objective: To increase the efficiency of early diagnosis of thrombophilic changes in the blood in patients with essential hypertension and concomitant obesity, combined with non-alcoholic fatty liver disease.Materials and methods. The study was conducted on the clinical base of the Department of Propedeutics of Internal Medicine No. 1 of the Bogomolets National Medical University in Kiev Clinical Hospital on railway transport No. 2 Branch «Center for Health Protection» of PJSC «Ukrainian Railway». 152 patients were examined: 72 men and 80 women. The patients were divided into groups: Group I – patients with stage II hypertension without signs of liver damage (46 people); Group II – patients with NAFLD without HT (54 people); Group III – patients with stage II HD with NAFLD (52 people).Results. In the group of NAFLD patients without concomitant hypertension, the effect of obesity was observed both on the platelet count and on their mean volume. The platelet count was significantly higher in the presence of obesity – it was 16 % (&lt;0.05) more, the MPV levels were also higher in NAFLD patients with a BMI ≥30 kg/m2 – by 2 % (p&lt;0,05). The degree of adrenaline-induced aggregation was significantly increased only in obese patients –– by 40 % (p&lt;0.001) compared with controls, and by 18 % with non-obese patients. During the exitox test in the NAFLD group in the obesity subgroup, a 9.5 % shortening of the clot formation time was revealed (p&lt;0.05). In the group of combined course of NAFLD and HT II stage the division of patients by BMI made it possible to reveal the depression of anticoagulant activity of antithrombin III was less by 10.5 % (p&lt;0.01), and protein C by 23.2 % (p&lt;0.001) in obese patients.Conclusion. Addition of obesity to hypertension and to the comorbid course of hypertension with NAFLD increased the thrombogenic activity of the blood, affecting various stages of hemostasis. However, the indicators of platelet-plasma hemostasis in patients with independent NAFLD did not actually differ from patients with obesity and BM I&lt;30 kg/m2, which indicates similar pathophysiological mechanisms of prothrombotic changes in obesity and NAFLD.

Prothrombotic Changes in Patients with End-Stage Renal Disease and its Relation to Thrombotic Cardiovascular Complication

Background: There is a great risk of cardiovascular disease (CVD) and vascular thrombosis in patients with End-Stage Renal Disease (ESRD). These patients exhibit numerous abnormalities in coagulation, fibrinolytic, inhibitory protein abnormalities in multiple levels. Aim: To assess hypercoagulable changes by measuring the levels of Antithrombin, plasma fibrinogen and FXII activity in patients with ESRD, and to found correlation between and hematological parameters including: Hb level, WBC count, reticulocyte percentage and platelet count. Method: A case control study conducted at Al-Hayat center, Al Karama teaching hospital during the period from the 1 of February to the 30 of October 2014 and 50 patients aged < 60 years of both genders with (ESRD) in addition to 20 apparently healthy controls were included in this study. Results: Patients and controls were matched for age and gender. The mean hemoglobin level, total WBC count, absolute neutrophil count, reticulocyte percentage and platelets count were significantly lower in ESRD patients than controls, P<0.05. The mean values of the coagulation parameters, ProthrombinTtime (PT), Activated Partial Thromboplastin Time (APTT), Plasma Fibrinogen and Factor XII activity were significantly higher in patients than controls. Anti-thrombin activity was significantly lower in patients group than controls, (P<0.001). Cardiovascular complications and vascular thrombosis included Deep Venous Thrombosis( DVT), Cerebro-Vascular-Accident (CVA), Myocardial Infarction (MI), angina or heart failure reported in 62% of the patients. Patients with cardiovascular complication and vascular thrombosis had significantly higher PT, APTT, and factor XII activity, lower anti-thrombin activity as compared to those without cardiovascular complication and vascular thrombosis. Conclusion: (ESRD) patients had coagulation abnormalities render them more liable to have cardiovascular complications and vascular thrombosis.

Thromboinflammation and the hypercoagulability of COVID‐19

Thromboinflammation and the hypercoagulability of COVID‐19

COVID-19-associated coagulopathy: review of current recommendations for diagnosis, treatment and prevention

The coronavirus infection COVID-19 is a highly contagious disease caused by the SARS-CoV-2 virus. Specific prothrombotic changes of the hemostasis system in COVID-19 are associated with increased incidence of venous thromboembolic complications. The article is a literature review on the diagnosis, treatment and prevention of coagulopathy and venous thromboembolic complications associated with COVID-19. 11 studies evaluating the frequency of registration of venous thromboembolic complications and 11 clinical recommendations on correction of coagulopathy published before May 22, 2020 have been studied. The frequency of venous thromboembolic complications was unexpectedly high: 8-13% in the general ward and 9-18% in the intensive care unit against the background of preventive measures. Preventive doses of anticoagulants, low-molecular weight heparins or unfractionated heparin are indicated to all hospitalized patients. Prolonged prophylaxis after discharge from hospital can be recommended for those at high risk of venous thromboembolic complications and low risk of bleeding. An increase in D-dimer may be considered as an indication for instrumental detection of venous thromboembolic complications. If there is a suspicion of venous thromboembolic complications, anticoagulant therapy at therapeutic doses can be started before the diagnosis is confirmed: during inpatient treatment preference should be given to low-molecular heparin or unfractionated heparin, after discharge from hospital it is recommended to transfer to direct oral anticoagulants for a period of at least 3 months. Routine prevention of venous thromboembolic complications in ambulatory patients is not recommended.

Гемостаз у лиц с сахарным диабетом 2‑го типа и ожирением при острой и хронической цереброваскулярной патологии

Введение. В настоящее время цереброваскулярные заболевания (ЦВЗ) в России являются второй по частоте причиной смерти среди больных сахарным диабетом (СД). С гипергликемией и избыточной массой тела связывают протромботические и провоспалительные изменения, приводящие к неблагоприятным исходам инсульта и прогрессированию ЦВЗ. Цель исследования: оценить роль избыточной массы тела как дополнительного фактора риска развития нарушений гемостаза при острых и хронических формах цереброваскулярной патологии у пациентов с СД 2‑го типа (СД‑2). Материалы и методы. В исследование включено 305 пациентов с ишемическими ЦВЗ: группа 1 — 87 больных с ишемическим инсультом (ИИ) и СД‑2; группа 2 — 58 пациентов с ИИ без СД; группа 3 — 80 больных с хроническими ЦВЗ (ХЦВЗ) и СД‑2; группа 4 — 80 пациентов с ХЦВЗ без СД. Выполнены общесоматический и неврологический осмотр, магнитно-резонансная томография головного мозга, инструментальные исследования с расчетом индекса массы тела (ИМТ) и лабораторные исследования с определением гликемии и гликированного гемоглобина (HbA1c), АДФ-индуцированной (АДФ-АТ) и адреналин-индуцированной (Адр-АТ) агрегации тромбоцитов, коагулограммы, включающей содержание фибриногена и Д-димеров, международное нормализованное отношение, активированное частичное тромбопластиновое время, фибринолитическую активность (ФА), индекс фибринолиза, активность плазминогена и уровень тканевого активатора плазминогена (t-РА). Результаты. Наибольших значений глюкоза и HbA1c достигали у пациентов с ИИ и СД‑2. Во всех группах больных с цереброваскулярной патологией СД‑2 сопровождался ожирением и повышенным ИМТ. ЦВЗ (как ИИ, так и хроническая форма) в сочетании с СД‑2 протекали на фоне протромботического состояния крови, связанного с нарушением всех звеньев гемостаза, и проявлялись увеличением АДФ-АТ и Адр-АТ, повышением содержания фибриногена и Д-димеров при одновременном снижении ФА, индекса фибринолиза, активности плазминогена и уровня t-PA. Самые выраженные нарушения наблюдали у пациентов с ИИ и СД‑2, особенно со стороны фибринолиза. Выявлены значимые корреляции между ИМТ и агрегацией тромбоцитов, уровнями фибриногена и Д-димеров, ФА и t-PA. Заключение. У лиц с СД‑2 острые и хронические ЦВЗ сопровождаются ожирением и увеличенным ИМТ, который взаимосвязан с активацией тромбоцитарного и плазменного гемостаза и снижением фибринолиза. Наибольшие изменения отмечены у пациентов с острым инсультом и СД‑2, для которых характерно сочетание гиперфибриногенемии и значительное снижение фибринолиза. Повышение ИМТ у больных ЦВЗ ассоциировано с выраженностью протромботических изменений. Introduction. At present cerebrovascular diseases (CVD) in Russia is the second most common cause of death among patients with diabetes mellitus (DM). Prothrombotic and pro-inflammatory changes leading to adverse outcomes of stroke and progression of CVD are associated with hyperglycemia and obesity. Aim: to assess the role of obesity as an additional risk factor for the development of hemostasis disorders in acute and chronic forms of cerebrovascular pathology in patients with type 2 diabetes mellitus (DM‑2). Materials and methods. The study included 305 patients with ischemic CVD: group 1 — 87 patients with ischemic stroke (IS) and DM‑2; group 2 — 58 patients with IS without DM; group 3 — 80 patients with chronic CVD (CCVD) and DM‑2; group 4 — 80 patients with CCVD without DM. The following studies were completed: somatic and neurological examinations, magnetic resonance imaging of the brain, calculation of body mass index (BMI) and laboratory tests with the determination of glycemia and glycated hemoglobin (HbA1c), ADP-induced (ADP-AT) and adrenaline-induced (Adr-AT) platelet aggregation, coagulogram with fibrinogen and D-dimers content, international normalized ratio, activated partial thromboplastin time, fibrinolytic activity (FA), fibrinolysis index (FI), plasminogen activity and level of tissue plasminogen activator (t-PA). Results. The highest values of glucose and HbA1c were found in patients with IS and DM‑2. In all groups of patients with cerebrovascular pathology DM‑2 was accompanied with obesity and increased BMI. CVD (both IS and chronic form) in combination with DM‑2 were accompanied by prothrombotic blood state (associated with hemostasis disorders), and manifested by enhancement of ADP-AT and Adr-AT, increasing of fibrinogen and D-dimers content and decreasing of FA, FI, plasminogen activity and t-PA. Most expressed disturbances (especially in fibrinolysis) were observed in patients with IS and DM‑2. Significant correlations were found between BMI and platelet aggregation, levels of fibrinogen and D-dimers, FA and t-PA. Conclusion. In patients with DM‑2 acute and chronic CVD are accompanied by obesity and increased BMI and associated with activation of platelet and plasma hemostasis and decreased fibrinolysis. The largest changes were noted in patients with acute stroke and DM‑2 and characterized by a combination of hyperfibrinogenemia and a significantly decreased fibrinolysis. Increasing of BMI in patients with CVD was associated with the severity of prothrombotic changes.

In vitro Fertilization Procedures with Embryo Transfer and Their Association with Thrombophilia, Thrombosis and Early Antithrombotic Treatments.

In vitro fertilization (IVF) procedures have been frequently associated with antithrombotic treatments, in particular, to aspirin or low-molecular-weight heparin (LMWH). The rationale of this treatment is based on the increase of thrombotic risk occurring in this clinical context. Indeed, both prothrombotic changes of coagulation parameters specifically related to IVF procedures as well as the presence of potential thrombophilic alterations may concur to increase the risk in these women. Furthermore, the presence of thrombophilia has been suggested as a potential cause of recurrent IVF failures. Therefore, antithrombotic treatments have been historically planned to prevent thrombotic disorders during pharmacological ovarian stimulation and/or to increase a successful rate of pregnancy and live births after IVF with embryo transfer. However, up to date, the role of inherited and\\or acquired thrombophilia is still debated as well as a univocal therapeutic approach is lacking in women with infertility. The administration of antithrombotic drugs differs in several studies and even the dosages of aspirin and\\or low-molecular-weight heparin are different. This review focuses on underlining current evidence on the role of thrombophilia and thromboprophylaxis in women selected for IVF with embryo transfer.

Study of Prothrombotic Changes in Metabolic Syndrome.

The metabolic syndrome is a complex disorder of various metabolic risk factors in a single individual having central obesity and commonly associated with diabetes and cardiovascular diseases. The aim of our study was to study the relationship between coagulation abnormalities and metabolic syndrome. We performed a prospective cross-sectional study in a tertiary care hospital. A total of fifty cases of metabolic syndrome and fifty age & sex matched controls were selected. These two groups were investigated for Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Fibrinogen levels, Plasminogen Activator Inhibitor 1(PAI1) levels and Factor VIII levels. In cases with metabolic syndrome, significantly increased levels of Fibrinogen, Factor VIII and Plasminogen Activator Inhibitor1 (PAI1) were observed. PT & APTT were shorter in cases with metabolic syndrome. The coagulation parameters studied, correlated significantly with the components of metabolic syndrome. Metabolic syndrome is a hypercoagulable state and further studies are required for further evaluation of the consequences of this hypercoagulable state. There is a need for clinical trials evaluating prophylactic anticoagulation for prevention of venous thrombosis in patients with metabolic syndrome.

Coronavirus Disease 2019, Prothrombotic Factors, and Venous Thromboembolism.

Coronavirus disease 2019 (COVID-19) is causing devastating morbidity and mortality worldwide. Several studies have shown that the severely ill patients have high or very high D-dimer values, and a hypercoagulable state has been described with, in some cases, development of disseminated intravascular coagulation (DIC). A few reports have indicated that there seems to be a higher incidence of venous thromboembolism than expected in otherwise severely ill patients. In this article, we will discuss the prothrombotic changes observed and to what extent they are specific for COVID-19. The incidence of thromboembolic events will be compared with those reported in sepsis and severe influenza A H1N1. The emphasis is on venous events, which have been the most frequently reported events. Finally, the intensity of pharmacological prophylaxis against venous thromboembolism will be discussed.

Patients with paroxysmal nocturnal hemoglobinuria demonstrate a prothrombotic clotting phenotype which is improved by complement inhibition with eculizumab.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder, characterized by complement-mediated intravascular hemolysis and thrombosis. The increased incidence of PNH-driven thrombosis is still poorly understood, but unlike other thrombotic disorders, is thought to largely occur through complement-mediated mechanisms. Treatment with a C5 inhibitor, eculizumab, has been shown to significantly reduce the number of thromboembolic events in these patients. Based on previously described links between changes in fibrin clot structure and thrombosis in other disorders, our aim was to investigate clot structure as a possible mechanism of thrombosis in patients with PNH and the anti-thrombotic effects of eculizumab treatment on clot structure. Clot structure, fibrinogen levels and thrombin generation were examined in plasma samples from 82 patients from the National PNH Service in Leeds, UK. Untreated PNH patients were found to have increased levels of fibrinogen and thrombin generation, with subsequent prothrombotic changes in clot structure. No link was found between increasing disease severity and fibrinogen levels, thrombin generation, clot formation or structure. However, eculizumab treated patients showed decreased fibrinogen levels, thrombin generation and clot density, with increasing time spent on treatment augmenting these antithrombotic effects. These data suggest that PNH patients have a prothrombotic clot phenotype due to increased fibrinogen levels and thrombin generation, and that the antithrombotic effects of eculizumab are, in-part, due to reductions in fibrinogen and thrombin generation with downstream effects on clot structure.

SAT-LB94 An Unusual Case of Acute Myocardial Infarction Revealing Underlying Polycythemia Secondary to Exogenous Bioidentical Testosterone Therapy

BACKGROUND: Many patients seeking testosterone therapy are turning to compound pharmacies for customized bioidentical testosterone replacement. These pharmacies market “bioidentical” hormone therapies as more effective and superior to traditional FDA-approved synthetic therapies. Bioidentical formulations are available as injections, creams, and subcutaneous pellet implants. Exogenous testosterone replacement is associated with polycythemia complicated by increased blood pressure, blood viscosity, and platelet aggregation (1). The ensuing hypercoagulable and prothrombotic changes predispose individuals to adverse cardiac events, including myocardial infarction.CLINICAL CASE: A 66-year-old male with hypertension, type 2 diabetes, and hyperlipidemia presented with chest pain and dizziness. Initial EKG was unremarkable but troponin levels were elevated and the patient was admitted to telemetry. Lexiscan indicated anterior territory ischemia and coronary angiography revealed 95% stenosis of the left anterior descending artery (LAD). He underwent percutaneous coronary intervention (PCI) with stenting of the LAD. During the patient’s workup, he was noted to have elevated hemoglobin (20) and hematocrit (60) levels and was treated with 1g hydroxyurea as phlebotomy was unavailable. JAK2 mutation and EPO level screenings were ordered and unremarkable. The patient was noted to have multiple subcutaneous testosterone pellets in his buttocks which he stated were implanted three weeks prior. Serum total testosterone was elevated at 1226 ng/dL. Hematology was consulted and the patient continued daily 1g hydroxyurea. After discharge, the patient continued outpatient follow up with hematology and received plasmapheresis for management of polycythemia.CONCLUSION: Considering polycythemia can arise secondary to exogenous testosterone use and is a known risk factor for cardiovascular events, it is likely this patient’s myocardial infarction was complicated by his use of exogenous bioidentical testosterone. Compound pharmacies providing bioidentical testosterone are not required to report adverse events, provide black box warnings, or show evidence-based safety and efficacy profiles for their products. The increasing availability and use of non-FDA-approved testosterone therapies warrants increased physician vigilance, particularly for patients with existing cardiac conditions or predisposition to hypercoagulable and prothrombotic states. The lack of regulation and research in the realm of compound pharmacy hormone products calls for further studies and reforms to protect patients from the risk of developing detrimental complications.REFERENCE: (1) Xu, L., Freeman, G., Cowling, B. et al. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med11, 108 (2013).