Prothrombotic Coagulation Research Articles

Thromboelastography with Platelet Mapping Identifies High Platelet Reactivity is Associated with Obesity, Diabetes, and Thrombotic Events

Metabolic comorbidities such as diabetes and obesity are considered pro-inflammatory states which theoretically increase the risk of perioperative thrombotic events across many surgical disciplines. Currently, there is a paucity of objective metrics to determine such risk and ideal pharmacologic targets. Thromboelastography with Platelet Mapping (TEG-PM) provides a comprehensive profile of coagulation and may provide insight into clot dysregulation. Patients undergoing lower extremity revascularization underwent serial TEG-PM analysis. The relationship between the TEG-PM metrics and thrombosis was evaluated. Preoperative TEG-PM samples of patients with body mass index (BMI)≥25 were compared to those of patients with a normal BMI, and between patients with diabetes mellitus (DM) and those without. 218 TEG-PM samples from 202 patients were analyzed. The BMI≥25 cohort showed significantly greater platelet aggregation [81.9% (±20.9) vs. 68.6% (±27.7), P<0.01]. Patients with DM were more frequently on full-dose anticoagulation [47.7% vs. 29.7% P=0.01] yet demonstrated increased clot strength, or adenosine diphosphate (ADP)-Maximum Clot Amplitude (MA) [49.1 (±16.1) vs. 41.5 (±17.1) and 37.7 (±19.6) vs. 31.6 (±17.4) P<0.01]. 49 patients experienced thrombosis and exhibited greater platelet aggregation [76.6% (±17.8) vs. 66.8% (±30.4) P=0.03] and greater ADP/arachidonic acid MA [47.1 (±16.6) vs. 41.9 (±18.8) and 38.2 (±17.8) vs. 32.5 (±19.9) both P=0.05]. Patients who thrombosed were more often diabetic [69.5% versus 51.0% P=0.03] and on full-dose anticoagulation [75.0% vs. 56.8% P=0.02]. Patients with a BMI≥ 25 and those with diabetes demonstrated TEG-PM profiles similar to patients with thrombosis. Diabetes was independently associated withthrombosis, and full-dose anticoagulation was not protective. This suggests the potential utility of TEG-PM for thrombotic risk stratification based on metabolic factors and suggests antiplatelet agents may be effective at prevention of thrombotic events in this population.

Pulmonary embolism at CT pulmonary angiography in patients with COVID-19 at a tertiary care center in Nepal: a cross-sectional study.

This cross-sectional study was performed to evaluate the patients who tested positive for COVID-19 and underwent CTPA. COVID-19 infection in participants was confirmed by a PCR of nasopharyngeal or oropharyngeal swab samples. Frequencies of computed tomography severity scores and CTPA were calculated and compared with clinical and laboratory findings. The study included 92 patients with COVID-19 infection. Positive PE was found in 18.5% of the patients. The mean age of the patients was 59.83±13.58 years with an age range of 30-86 years. Among the total participants, 27.2% underwent ventilation, 19.6% died during treatment, and 80.4% of them got discharged. PE was developed in patients who did not receive prophylactic anticoagulation, which is statistically significant (P≤0.001). There was also a significant relationship between mechanical ventilation and CTPA findings. The authors conclude from their study that PE is one of the complications of COVID-19 infection. Rising D-dimer during the second week of disease alerts clinicians to do CTPA to exclude or confirm PE. This will help in the early diagnosis and treatment of PE.

Body Mass Index and Waist Circumference as Determinants of Hemostatic Factors in Participants of a Population-Based Study.

Background: In contrast to studies in patients, an association between obesity and blood coagulation factors has not been established in the population. If confirmed it could become a target for primary prevention. Objective: To investigate the relationship between Body Mass Index (BMI) and waist circumference (WC) with plasma concentrations of antithrombin III, D-dimers, fibrinogen D, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value, and international normalized ratio (INR) in the general population. Materials and Methods: Participants of the Cooperative Health Research in the Region of Augsburg (KORA) S4 study who took part in the KORA Fit follow-up (2018-2019, aged 54-74 years) examination were eligible. Citrate plasma samples were collected in fasted participants. After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men) with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the association between BMI or WC with hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the prevalence of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol, and serum triglycerides. Results: In the multivariable models (with or without health conditions), significant positive associations with BMI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein S, and quick value, while INR and antithrombin III were inversely associated. Similar to BMI, WC was significantly associated with all hemostatic factors, except for aPTT. Conclusion: In this population-based study, both increasing BMI and WC affect the blood coagulation system. Thus, modification of a prothrombotic coagulation profile emerged as a potential target for primary prevention in obese subjects.

Use of Thromboelastography with Platelet Mapping to Identify Prothrombotic Coagulation Profiles in Patients with History of Cardiac Intervention Undergoing Lower Extremity Revascularization.

Patients with concomitant coronary and peripheral artery disease (CAD and PAD) are at significant risk for major adverse limb events (MALEs). Prevention of thrombosis in this population is of paramount importance. Identifying prothrombotic coagulation profiles in this cohort may facilitate targeted thromboprophylaxis. We compared coagulation profiles of those with CAD and PAD to those with PAD alone during the perioperative period of lower extremity revascularization. Patients undergoing lower extremity revascularization underwent thromboelastography-platelet mapping (TEG-PM) analysis preoperatively and at serial intervals for up to 6 months. Coagulation profiles of patients with significant CAD (defined as history of coronary artery bypass graft or percutaneous coronary intervention) and PAD were compared with those with PAD alone. MALE in the postoperative period was recorded. Four hundred seventy-seven TEG-PM samples from 114 patients were analyzed; 28.1% had a history of significant CAD. The incidence of atrial fibrillation was higher in this group. The significant CAD group had lower ADP-platelet inhibition, higher ADP-platelet aggregation, and greater maximum clot strength compared with patients with PAD alone. Patients with significant CAD were more frequently on full-dose anticoagulation, but less frequently on dual antiplatelet therapy; 28.1% of patients with significant CAD developed postoperative MALE compared with 22.9% of patients with PAD alone (p = 0.40). For both groups, patients who developed postoperative MALE demonstrated greater ADP-platelet aggregation and lower ADP-platelet inhibition. Patients with a history of significant CAD undergoing lower extremity revascularization demonstrated prothrombotic TEG-PM profiles, less frequent use of dual antiplatelet therapy, and greater rates of full-dose anticoagulation. Decreased platelet inhibition was also associated with postoperative MALE. This study underscores the potential utility of viscoelastic assays for coagulation profiling in complex cardiovascular patients.

Successful Treatment of Fulminant Myocarditis with Intracardiac Thrombus in COVID-19

IntroductionThe treatment of pediatric patients with COVID-19 associated myocardial injury and prothrombotic coagulation derangements remains to be established. We cared for an adolescent with COVID-19 and fulminant myocarditis who required veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Her course was complicated by a large intracardiac thrombus, which was successfully treated with systemic tissue plasminogen activator (tPA).Case ReportA 17 year old unvaccinated female presented with fever and chest pain 7 days after testing positive for COVID-19. She had a peak troponin of 21.48 ng/ml, elevated brain natriuretic peptide (629 pg/ml), and severely diminished left ventricular systolic function. She progressed to cardiogenic shock and was cannulated to VA-ECMO via the neck. On ECMO day 2 while therapeutic on unfractionated heparin (UFH), a large thrombus was noted in the left ventricular apex, extending toward the aortic valve (Figure 1). Prior to this, she had no evidence of a deep vein thrombosis. Given the concern for an impending stroke upon restoration of ventricular function, a continuous systemic high-dose tPA infusion (0.1mg/kg/hr) was initiated, while she was continued on UFH. A twenty-fold increase in D-dimer levels and serial echocardiograms indicated a thrombolytic effect. After 22 hours of thrombolysis, the patient developed bleeding complications and tPA was discontinued. By ECMO day 4, the thrombus completely resolved. Once her bleeding was controlled, she was transitioned to bivalirudin. Cardiac function recovered by day 11 allowing for separation from ECMO. 25 days later, she was discharged without any neurologic deficits.SummaryThe coagulopathic derangements associated with COVID -19 pose significant challenges to the management of fulminant myocarditis. There are no guidelines regarding management of an intracardiac thrombus on ECMO. However, with careful monitoring, systemic tPA can be used to provide life-saving therapies with excellent neurological outcomes.

Idiopathic purpura fulminans associated with anti-protein S antibodies in children: a multicenter case series and systematic review

AbstractIdiopathic purpura fulminans (IPF) is a rare but severe prothrombotic coagulation disorder that can occur after chickenpox or human herpesvirus 6 (HHV-6) infection. IPF leads to an autoantibody-mediated decrease in the plasma concentration of protein S. We conducted a retrospective multicenter study involving patients with IPF from 13 French pediatric centers and a systematic review of cases in published literature. Eighteen patients were included in our case series, and 34 patients were included as literature review cases. The median age was 4.9 years, and the diagnostic delay after the first signs of viral infection was 7 days. The lower limbs were involved in 49 patients (94%) with typical lesions. In all, 41 patients (78%) had a recent history of varicella-zoster virus infection, and 7 patients (14%) had been infected by HHV-6. Most of the patients received heparin (n = 51; 98%) and fresh frozen plasma transfusions (n = 41; 79%); other treatment options were immunoglobulin infusion, platelet transfusion, corticosteroid therapy, plasmapheresis, and coagulation regulator concentrate infusion. The antithrombin level and platelet count at diagnosis seemed to be associated with severe complications. Given the rarity of this disease, the creation of a prospective international registry is required to consolidate these findings.

Lifestyle Intervention Improves Prothrombotic Coagulation Profile in Individuals at High Risk for Type 2 Diabetes.

Patients with obesity and insulin resistance are at higher risk for arterial and venous thrombosis due to a prothrombotic state. The present study addressed whether this is reversible by lifestyle intervention and elucidated potential underlying associations. A total of 100 individuals with impaired glucose tolerance or impaired fasting plasma glucose participated in a 1-year lifestyle intervention, including precise metabolic phenotyping and MRS-based determination of liver fat content as well as a comprehensive analysis of coagulation parameters before and after this intervention. During the lifestyle intervention, significant reductions in coagulation factor activities (II, VII, VIII, IX, XI, and XII) were observed. Accordingly, prothrombin time (PT%) and activated partial thromboplastin time (aPTT) were slightly decreased and prolonged, respectively. Moreover, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), and also protein C and protein S decreased. Fibrinogen, antithrombin, D-dimer, and FXIII remained unchanged. Searching for potential regulators, especially weight loss, but also liver fat reduction, improved insulin sensitivity, and decreased low-grade inflammation were linked to favorable changes in hemostasis parameters. Independent of weight loss, liver fat reduction (FII, protein C, protein S, PAI-1, vWF), improved insulin sensitivity (protein S, PAI-1), and reduced low-grade inflammation (PT%, aPTT, FVIII/IX/XI/XII, vWF) were identified as single potential regulators. Lifestyle intervention is able to improve a prothrombotic state in individuals at high risk for type 2 diabetes. Besides body weight, liver fat content, insulin sensitivity, and systemic low-grade inflammation are potential mechanisms for improvements in hemostasis and could represent future therapeutic targets.

Coronavirus disease 2019 and coagulopathy: other prothrombotic coagulation factors.

There is an increasing evidence supporting the existence of coagulopathy in coronavirus disease 2019 (COVID-19) patients. Most of reports are mainly focused on d-dimer. Our objective is to describe coagulation parameters in these patients that could be involved in a hypercoagulate state and to test platelet function to see if there are short closure times. We analyzed coagulation samples from 80 patients admitted with COVID-19 in our hospital. We also tested platelet function by closure times in a small subgroup of patients. Most of samples had increased d-dimer (96.2%) (median of d-dimer: 1158 ng/ml FEU), increased fibrinogen (75.2%) (median: 5.23 g/l), increased factor VIII (86%) (median: 264.8 U/dl), decreased protein S (22.5% of women, 62.5% of men) (median: 62.8 and 68.5 U/dl, respectively), decreased protein C (7.6%) (median: 100 U/dl), decreased factor XII (25.3%) (median: 90.3 U/dl) and decreased antithrombin activity (21%) (median: 86 U/dl). International normalized ratio was higher than normal in 24 patients (30%) (median: 1.13). The activated partial thromboplastin time ratio was below the normal range in nine patients (11.2%) and above normal in three (3.75%) (median: 0.93). The closure times were short in the 20% and 40% of samples of collagen and ADP and collagen and epinephrine, respectively. Twelve of the 80 patients (15%) had a thrombotic event and all had several abnormal coagulation parameters related with increased thrombotic risk. The results of this study support a hypercoagulability state in COVID-19 patients and it may help to explain the microvascular thrombosis caused by the inflammatory response.

Biomarkers of liver dysfunction correlate with a prothrombotic and not with a prohaemorrhagic profile in patients with cirrhosis

Background & AimsDifferent liver dysfunction biomarkers are used to assess the bleeding risk of patients with cirrhosis, either as such or included in bleeding risk assessment scores. Since the current model of coagulation in patients with cirrhosis describes a procoagulant tendency with increasing severity according to Child-Pugh stage, we decided to investigate the relation between liver dysfunction biomarkers and thrombin generation. Our aim was to verify their adequacy for bleeding risk assessment.MethodsWe performed a prospective single-centre study including 260 patients with liver cirrhosis. Thrombin generation was measured using ST Genesia® Thrombin Generation System without and with thrombomodulin in order to assess the role of proteins C and S. Relations between thrombin generation and Child-Pugh/model for end-stage liver disease (MELD) scores, prothrombin time (PT)/international normalised ratio (INR), activated partial thromboplastin time (aPTT), factor V activity, albumin, and total bilirubin were assessed.ResultsThrombomodulin-mediated inhibition of thrombin generation was significantly decreased in patients with liver cirrhosis compared with healthy donors (p <0.0001) and in Child-Pugh B and C compared with A (p <0.0001 [A–B], 0.4515 [B–C], <0.0001 [A–C]). Thrombomodulin-mediated inhibition significantly decreased with increasing PT/INR, aPTT, and total bilirubin levels and with decreasing factor V activity and albumin levels.ConclusionsWorsening liver dysfunction biomarkers reflect an increasing prothrombotic profile in patients with liver cirrhosis. In particular, prolonged PT/INR and aPTT as well as decreasing factor V activity are related to an increasing thrombotic risk and not to an increasing bleeding risk. These parameters should not be used to assess bleeding risk due to haemostatic anomalies in patients with liver cirrhosis. Alternative biomarkers for bleeding risk assessment in patients with liver cirrhosis need to be developed.Lay summaryWe demonstrate that the laboratory parameters used to assess bleeding risk of patients with liver disease, e.g. prothrombin time/international normalised ratio (PT/INR) and activated partial thromboplastin time (aPTT), are inadequate for this purpose because they are correlated with a prothrombotic coagulation profile. In this article, we highlight the need for alternative parameters to assess bleeding risk in patients with liver disease.

Diabetes and atherothrombosis: The circadian rhythm and role of melatonin in vascular protection.

Obesity-related euglycaemic insulin resistance clusters with cardiometabolic risk factors, contributing to the development of both type 2 diabetes and cardiovascular disease. An increased thrombotic tendency in diabetes stems from platelet hyperactivity, enhanced activity of prothrombotic coagulation factors and impaired fibrinolysis. Furthermore, a low-grade inflammatory response and increased oxidative stress accelerate the atherosclerotic process and, together with an enhanced thrombotic environment, result in premature and more severe cardiovascular disease. The disruption of circadian cycles in man secondary to chronic obesity and loss of circadian cues is implicated in the increased risk of developing diabetes and cardiovascular disease. Levels of melatonin, the endogenous synchronizer of circadian rhythm, are reduced in individuals with vascular disease and those with deranged glucose metabolism. The anti-inflammatory, antihypertensive, antioxidative and antithrombotic activities of melatonin make it a potential therapeutic agent to reduce the risk of vascular occlusive disease in diabetes. The mechanisms behind melatonin-associated reduction in procoagulant response are not fully known. Current evidence suggests that melatonin inhibits platelet aggregation and might affect the coagulation cascade, altering fibrin clot structure and/or resistance to fibrinolysis. Large-scale clinical trials are warranted to investigate the effects of modulating the circadian clock on insulin resistance, glycaemia and cardiovascular outcome.

Study on Coagulation Factor VIII and Fibrinogen Levels in Patients with Thyroid Disorders.

Introduction:A kaleidoscope of coagulation disorders has been reported in patients with thyroid dysfunctions. Globally, these disorders involve both primary and secondary hemostasis and range from subclinical laboratory abnormalities to, more rarely, life-threatening hemorrhages or thrombotic events. While overt hypothyroidism appears to be associated with a bleeding tendency, hyperthyroidism emerged to have an increased risk of thrombotic events. As a controversy, subclinical hypothyroidism and mild hypothyroidism have been reported as prothrombotic state. The mechanisms involved in these observations are also not conformed.Objective:To study the levels of prothrombotic coagulation factor VIII and fibrinogen in patients with thyroid disorder at baseline and to correlate the change in these factors after attaining euthyroid state by treatment.Study Design:This was a longitudinal interventional study.Subjects and Methods:Forty patients were recruited based on the inclusion and exclusion criteria, and their coagulation profile (prothrombin time, aPTT, Factor VIII, and fibrinogen levels), routine hematological, and biochemical profile was done at baseline and 6 weeks after attaining euthyroid state.Results and Conclusion:Hyperthyroidism and mild hypothyroidism were found to be hypercoagulable states and moderate-to-severe hypothyroidism as hypocoagulable states. Nevertheless, further observational and intervention studies are needed to provide more definitive information on the clinical relevance of this association, along with the potential implication for prevention and treatment of coagulation/fibrinolytic abnormalities in patients with thyroid dysfunction.

Evaluation of hypercoagulability state in perinatal arterial ischemic stroke with rotation thromboelastometry.

Perinatal arterial ischemic stroke (PAIS) is an important cause of pediatric morbidity and mortality. The etiology of PAIS remains unknown. Several maternal-neonatal disorders, and especially prothrombotic risk factors, have been reported in infants with perinatal stroke (PS). Rotation thromboelastometry (ROTEM) can analyze the coagulation system, from the beginning of coagulation, through clot formation, and ending with fibrinolysis. The aim of this study was to evaluate the hypercoagulability state in PAIS patients using ROTEM. Patients were obtained by evaluating hospital files retrospectively. Twenty patients with PAIS and 19 healthy controls were included in the study. Prothrombotic risk factors and standard coagulation parameters were collected for all patients. Thromboelastometry (TEM) analysis was performed with the ROTEM® Coagulation Analyzer model Gamma 2500 (Tem International, Munich, Germany). Patients were separated into two groups; Group 1 included PAIS patients with prothrombotic risk factors and Group 2 included patients with no prothrombotic risk factors. Group 1 includes six patients and Group 2 includes fourteen. Maternal risk factors were reported in 55% and prothrombotic risk factors were detected in 30% of the patients. ROTEM analyses were done mean age of 11.2±9.4months. ROTEM analysis showed that maximum clot firmness (MCF) value on both groups was significantly higher than in the control group, which is consistent with a hypercoagulable state. There was no statistical difference between the MCF values of Group 1 and Group 2. No significant correlations were found between the ROTEM parameters and the hematological parameters. The etiology of PAIS is still unclear. Prothrombotic risk factors may be an important etiology for PAIS. However, standard hematological tests for evaluating prothrombotic risk factors are limited. In our study, ROTEM analyses showed higher maximum clot firmness in PAIS patients compared to controls. ROTEM analyses may suggest a hypercoagulable state due to abnormal fibrinolysis in PAIS patients. Normative data and further research is needed to validate our findings.

Novel copper (II) alginate hydrogels and their potential for use as anti-bacterial wound dressings

The incorporation of a metal ion, with antimicrobial activity, into an alginate dressing is an attractive approach to minimize infection in a wound. In this work, copper (II) cross-linked alginate hydrogels were successfully prepared using a two-step cross-linking procedure. In the first step, solid alginate films were prepared using a solvent-casting method from soft gels of alginate solutions that had been lightly cross-linked using a copper (II) (Cu2+) sulfate solution. In the second step, the films were further cross-linked in a corresponding Cu2+ sulfate solution using a dipping method to further improve their dimensional stability. Alginate solution (at 2%w/v) and Cu2+ sulfate solution (at 2%w/v) in acetate buffer at a low pH provided soft films with excellent swelling behavior. An increase in either Cu2+ ion concentration or cross-linking time led to hydrogels with more densely-cross-linked networks that limited water absorption. The hydrogels clearly showed antibacterial activity against Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis and Streptococcus pyogenes, which was proportional to the Cu2+ ion concentration. Blood coagulation studies showed that the tested copper (II) cross-linked alginate hydrogels had a tendency to coagulate fibrin, and possibly had an effect on pro-thrombotic coagulation and platelet activation. Conclusively, the prepared films are likely candidates as antibacterial wound dressings.

Increased prothrombotic property as a risk factor of acute kidney injury after surgical repair of abdominal aortic aneurysm: a prospective observational study.

BackgroundAcute kidney injury (AKI) is one of the major morbidities after surgical repair of abdominal aortic aneurysm (AAA); however, precise pathogenesis of this morbidity has not been well determined. Since prothrombotic coagulation abnormality may precede organ dysfunction in systemic inflammatory state, we examined the kinetics of von Willebrand factor (VWF) and a disintegrin-like metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13), a cleaving enzyme of VWF, on the development of AKI after AAA surgery.MethodsThe kinetics of ADAMTS13 and VWF were examined in ten patients who underwent surgical repair of AAA. The changes in plasma neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker for AKI, and serum creatinine concentration were also examined at four points until seventh postoperative day (POD). Clinical diagnosis of AKI was based on the change in serum creatinine concentration and urine output according to Acute Kidney Injury Network (AKIN) criteria.ResultsADAMTS13 activity was significantly lower than normal level before the surgery and showed a trend of decrease toward 3POD. The VWF/ADAMTS13 ratio showed a significant increase on 1POD, which persisted until 7POD. None of patents was diagnosed as AKI based on AKIN criteria, although two patients received furosemide and/or carperitide therapy because of decreased urine output less than 0.5 ml/kg/h for several hours in ICU. Plasma NGAL showed a trend to increase after the surgery, which was significant on 3POD. The change in plasma NGAL was significantly correlated with VWF/ADAMTS13 ratio (P < 0.01).ConclusionsThis study has shown that patients undergoing AAA surgery were prothrombotic after the surgery because of high VWF/ADAMTS13 ratio. Correlation between VWF/ADAMTS13 ratio and NGAL might indicate contribution of thrombotic event to subclinical AKI in the patients undergoing AAA surgery.

Differences in Coagulation between Hemodialysis and Peritoneal Dialysis

End-stage renal disease patients have significant cardiovascular morbidity and mortality, but little is known about differences in coagulation profiles between patients on hemodialysis (HD) and on peritoneal dialysis (PD). Given their long-term exposure to glucose-based dialysate, patients on PD can experience metabolic derangements. Theoretically, that exposure should create a more prothrombotic environment than occurs in HD patients. The objective of the present study was to quantify potential differences in baseline coagulation between PD and HD patients. ♢ Our single-center cross-sectional study at a large academic health science center enrolled 50 age-, race-, and sex-matched subjects (10 control subjects, 20 HD patients, and 20 PD patients). Measurements included platelet function, platelet receptor distribution, and coagulation dynamics by thromboelastography and Hemodyne hemostasis assay (Hemodyne, Richmond, VA, USA). ♢ Compared with healthy control subjects, patients on both forms of dialysis showed prothrombotic coagulation protein profiles. The tissue-factor pathway was markedly elevated in both groups, but PD was associated with significantly greater concentrations of tissue factor (p = 0.0056) and tissue-factor pathway inhibitor (p = 0.0138). Similarly, compared with patients receiving HD, patients on PD had greater concentrations of fibrinogen (p = 0.0325), which corresponded with platelet hyperfunction as measured by platelet contractile force and clot elastic modulus (p = 0.003 and 0.017 respectively, compared with values in HD patients). Platelet receptor distribution was similar between the groups. ♢ Compared with patients on HD, patients on PD appear to have a more prothrombotic profile. The clinical relevance of these findings needs to be studied in a prospective manner.

Heparin Induced Thrombocytopenia: Can Be Excluded

Thrombocytopenia is common in the hospitalized patients. Heparin induced thrombocytopenia (HIT) can be defined as clinicopathological procoagulant condition with thrombocytopenia in patients on heparin therapy. Platelet count of less than 100,000 or decrease by 50% of the base line value from 5-14 days of heparin therapy. In rare case HIT can occur before 5th day or after the 14th day or even after stopping the heparin therapy. HIT is a known but rare complication of heparin therapy. It is a potentially life and limb threatening, prothrombotic coagulation disorder associated with significant increased in the morbidity and mortality. Early and accurate diagnosis or exclusion of HIT is the corner stone in the management of these patients; as the over diagnosis will result in use alternative anticoagulant with increased bleeding risk or under diagnosis or delayed diagnosis will leaves patient vulnerable for the development of thrombosis. HIT have a unique pathophysiology and testing, and a low 4 ‘T’ Score, lateral flow immunoassay (LFIA) can rule-out HIT in 10 minutes. It has a unique complication profile: Thromboemboli, and unique management with the alternative anticoagulants; It is a unique thrombocytopenia, where the risk of thrombosis is more than that of bleeding.

Etiology of Perinatal Stroke; A Role for Prothrombotic Coagulation Factors?

Objective: Stroke is relatively rare in children and the clinical presentation of perinatal stroke is often subtle. In perinatal stroke, multiple, often coexisting, risk factors are involved, varying from maternal and fetal risk factors during pregnancy and delivery, to infectious causes and cardiac diseases as well as medical interventions and congenital prothrombotic coagulation factors.Methods: To explore the prevalence of different predisposing conditions in perinatal stroke patients we evaluated 96 patients (43 males; 53 females), including subjects with ischemic and hemorrhagic stroke subtypes. Baseline investigations included complete blood count, total cholesterol, triglycerides, lipoprotein (a), prothrombin, activated thromboplastin, plasma fibrinogen level, activity of protein C sensitivity ratio, total plasma homocysteine, lupus anticoagulant, anticardiolipin, and anti-β2 glycoprotein1 antibodies. DNA analysis was performed for the Factor V Leiden mutation, Factor II G20219A variant, and the thermolabile variant of MTHFR.Results: The major genetic risk factor in our series of patients was heterozygosity and homozigosity for the MTHFR C677T mutation (39/96 patients; 40%) in 5 patients was associated with the Factor V Leiden mutation, in 6 with deficiency of activity of protein C. Acquired predisposing conditions were present in 18/96 (18%) patients and included Threatened abortion, oligohydramnios, intra uterine growth retardation, gestosis, chorioamniositis. In 7 patients both genetic and aquired predisposing factors were present.Conclusion: Our results emphasize that prothrombotic coagulation risk factors, especially MTHFR mutation, can predispose to perinatal stroke, alone or in combination with other genetic or acquired factors.

Prothrombotic Coagulation Factors (PTCF) in Symptomatic Neonatal Cerebral Infarction (SNCI). What is their Role?

Background: PtCFs have been associated with SNCI, but their relative risks is still unknown.Objective: To examine the extent to which single and combined PtCF influence the onset of SNCI.Methods: Prospective multicenter case-control study. Factor V (FV) G1691A mutation; Prothrombin (PT) G20210A variant; MTHFR T677T genotype; Antithrombin III (AT); Protein C; Protein S; Lipoprotein (Lp-a); Homocystein and anticardiolipin antibodies were investigated in 29 infant-mother pairs with SNCI and in 28 infant-mother control pairs.Results: Eight of 29 patients (28%) had at least 1 PtCF compared with 9/28(33%) controls. PtCF were found in 17(58%) mothers of infants with infarction and in 9(36%) of mothers of healthy infants (OR 2,1, 95%CI 0,7-6,4). At least 2 factors were found in 2 neonates; one SNIC patient and one healthy control. Two mothers of a SNIC patient and a control, respectively, had at least 2 factors. Table Table Full size table Conclusion: Our data indicate that PtCF do not appear to play a major role in SNCI.

Venous Thromboembolism with Chronic Liver Disease

Background Patients with chronic liver disease have both antithrombotic and prothrombotic coagulation abnormalities. Published data conflict on whether patients with chronic liver disease have a high or low prevalence of venous thromboembolism. Methods The number of patients discharged from hospitals throughout the US with a diagnostic code for chronic alcoholic and chronic nonalcoholic liver disease from 1979 through 2006 was obtained from the National Hospital Discharge Survey. We compared prevalences of venous thromboembolism among patients with chronic alcoholic liver disease and chronic nonalcoholic liver disease. Results Among 4,927,000 hospitalized patients with chronic alcoholic liver disease from 1979-2006, the prevalence of venous thromboembolism was 0.6%, compared with 0.9% among 4,565,000 hospitalized patients with chronic nonalcoholic liver disease. Conclusion The prevalence of venous thromboembolism in hospitalized patients with chronic liver disease, both alcoholic and nonalcoholic, was low. The prevalence of venous thromboembolism was higher in those with chronic non-alcoholic liver disease, but the difference was small and of no clinical consequence. Based on the literature, both showed a lower prevalence of venous thromboembolism than in hospitalized patients with most other medical diseases. It may be that both chronic alcoholic liver disease and chronic nonalcoholic liver disease have protective antithrombotic mechanisms, although the mechanisms differ.

The Balance between von-Willebrand Factor and its Cleaving Protease ADAMTS13: Biomarker in Systemic Inflammation and Development of Organ Failure?

This review investigates and highlights the activity of Willebrand factor (VWF) and its cleaving protease as biomarkers of the development of multiple organ dysfunction in infectious and noninfectious systemic inflammatory response syndrome. Ultra-large VWF (ULVWF) multimers activate platelets resulting in a prothrombotic situation. Systemic inflammation is associated with increased ULVWF plasma level and a decreased ADAMTS13 activity. The potential role of ADAMTS13 as a diagnostic and prognostic marker of disseminated intravascular coagulopathy is largely underestimated. VWF is an acute phase protein and its plasma level increases in systemic inflammation. When released from endothelial cells and platelets, the native multimeric glycoprotein is mostly present in the ultralarge form (ULVWF), which may have a major clinical significance under proinflammatory conditions. ULVWF-multimers may activate endothelial cells and platelets simultaneously. The multimers undergo limited proteolysis by a specific plasma metalloprotease known as ADAMTS13 (a disintegrin and metalloprotease with thrombospondin motif), thus, in healthy individuals only marginal amounts of circulating ULVWF are detectable. Severe hereditary or acquired ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura (TTP), which contributes to prothrombotic coagulation abnormalities preceding organ dysfunction systemic inflammatory response syndrome (SIRS). In proinflammatory conditions, ADAMTS13 activity decreases due to various mechanisms, (i) down regulation on a transcriptional level, (ii) proteolytic degradation, and (iii) consumption due to the high substrate level. Marked dysbalance as found in patients with severe sepsis or septic shock results in substantial amounts of plasma ULVWF. This level of dysbalance is negatively correlated with platelet count and positively correlated with the severity of inflammation and the degree of organ failure.