Hemostasis and Thrombosis

As part of the multifactorial role of liver in protein synthesis, many coagulation factors, natural anticoagulants, and compounds of the fibrinolytic system are produced in the liver. A prolonged liver disease, either biliary obstruction or parenchymal liver disease, is consecutively accompanied by abnormal clotting.
In the present paper we review the haemostasis impairment in obstructive jaundice with special reference to the hepatic cirrhosis and failure, to systemic inflammation and sepsis that develops in cholestatic diseases, and finally in some other benign or malignant diseases including pancreatic adenocarcinoma, acute pancreatitis,
cholangiocarcinoma, and hepatocellular carcinoma. Finally, a special reference to the possible therapeutic interventions has been made. The aim of the present review is to collect the current concepts concerning the haemostasis impairment in obstructive jaundice and provide practical guidelines for the diagnostic and therapeutic strategies. Understanding the pathophysiology of haemostatic changes in patients
with cholestasis, and, more generally, liver disease, is the hallmark of accurate diagnosis and treatment.

We report a case of spinal epidural hematoma (SEH) preceded by diagnostic lumbar puncture (LP) in a 5-year-old boy with acute lymphoblastic leukemia. MRI confirmed the presence of SEH between T7 and L5 levels, but the patient showed fast recovery during the next hours and conservative management was elected.

First responders are sometimes confronted with external uncontrolled haemorrhage despite compression, bandages, and tourniquets. Several topical haemostatic agents were developed to try to face these situations. Their application was mainly described and studied in military environment. We report the case of a worker victim of an accident of construction site with hemorrhagic perineal trauma for whom the use of a haemostatic bandage QuikClot ACS+™ (Z-Medica) seemed to us particularly useful in prehospital setting.

Haemorrhage, massive transfusion and coagulopathy are the most important
factors affecting outcome in severely injured patients. More than
50 per cent of patients with massive hemorrhage die, and for those who
die within hours of the injury event, it is often the most common cause of
death. Recent research has led to a new appreciation of the central role
of coagulopathy in trauma care.
An acute traumatic coagulopathy has been identified relatively recently.
Developing early in the postinjury phase, it is present at admission in one
of four trauma patients and is associated with a four-fold increase in
mortality. Acute coagulopathy of trauma occurs in patients with shock
and is characterized by systemic anticoagulation and hyperfibrinolysis.
There is evidence that implicate activation of the protein C pathway in
this process. Control of bleeding is extremely challenging in the presence
of an established coagulopathy.
In current clinical practice, coagulopathy treatment remains widely varying
and often ineffective. Increasing availability of point-of-care devices has
encouraged new concept for managing massive blood loss. Modern
transfusion strategies are based on bedside coagulation monitoring with
specific real time goal-directed administration of antifibrinolytics, coagulation
factor concentrates, and blood products in modified ratio.

Abstract
Background and rationale: Diagnosis and treatment of a wide spectrum of abnormalities in the coagulation system in patients suffering from cirrhosis still remain a challenge to physicians. Using endogenous thrombin potential (ETP) method and thromboelastometry, we assessed coagulation profile in 60 adult patients with alcoholic cirrhosis and 50 healthy subjects. We evaluated coagulation profile of patients with these global hemostatic methods, link between ETP/thromboelastometry profiles and standard coagulation tests, relationship between ETP and thromboelastometry parameters with different degrees of liver lesions and correlation between these assays and biochemical liver function.
Main results: In most patients, ETP parameters were consistent with the hypocoagulable profile. The majorities of patients were identified as having decreased Cmax (n=55/60) and AUC (n=49/60) as well as increased t-lag values (n=39/60). There was significance between ETP parameters in two groups (p<0.001). The t-lag was higher in cirrhosis (30.1±10.8 vs. 25.6±14.2s). Both Cmax (peak height) and AUC (area under the curve) were higher in controls (112.0±20.9 vs. 98.3±10.9%; 68.3±28.2 vs. 67.9±16.4%). AUC correlated with cholinesterase (r=0.610; p<0.001), albumin (r=0.462; p<0.001), and total bilirubin (r=-0.281; p=0.031). Using thromboelastometry, we found hypocoagulability represented by reduced MCF (maximum clot firmness) in 33.3% (n=20/60) of patients in extrinsic, and 41.7% (n=25/60) of patients in intrinsic activated test. In patients, CFT (clot formation time) values were significantly higher, whereas MCF values were lower (extrinsic test: 116.6±45.6 vs. 79.2±16.9s; 55.9±8.9 vs. 66.2±4.0mm; p<0.001) compared to controls. There was a weak correlation (r=0.272; p=0.037) between cholinesterase activity and MCF in extrinsic test.
Conclusion: ETP may be an additional alternative for estimating impairment of synthesis liver function and severity degree of cirrhosis caused by alcohol. Thromboelastometry is superior to ETP for investigating coagulopathy in cirrhosis as it provides supplemental information such as maximum clot firmness and stability.
Keywords: Global hemostatic methods; Hepatic disease

Surgical removal of the spleen, splenectomy, is a procedure that has significantly decreased in frequency as our understanding of the infectious complications of the asplenic state increased. The full spectrum and details of splenic function, however, have yet to be fully outlined. As a result, our comprehension of the long-term consequences of splenectomy remains incomplete. We review the evidence relating to the effects of splenectomy on infection, malignancy, thrombosis, and transplantation. Perhaps the best-defined and most widely understood complication of splenectomy is the asplenic patient's susceptibility to infection. In response to this concern, novel techniques have emerged to attempt to preserve splenic function in those patients for whom surgical therapy of the spleen is necessary. The efficacy of these techniques in preserving splenic function and staving off the complications associated with splenectomy is also reviewed in this article.

Objectives/Hypothesis: Bleeding during endoscopic sinus surgery and open surgeries can easily obstruct the surgeons' field of view and increase morbidity and risk of intraoperative complications. Intraoperative bleeding could potentially be addressed by a hemostatic agent that safely disperses itself through the escaping blood. We tested the safety and efficacy of a self-propelling formulation of thrombin and tranexamic acid (SPTT) in stopping bleeding in a paranasal sinus injury and in an open surgical carotid injury sheep model. Study Design: Interventional animal study. Methods: SPTT was tested in the sinonasal space following endoscopic injury to the inferior turbinate of six sheep, and to the common carotid artery following open surgical injury in eight sheep. In the nasal cavity, bleeding time and local inflammation were measured and compared to plain gauze. Following carotid arteriotomy, successful hemostasis and markers of thrombosis and coagulopathy were compared to Floseal. Results: SPTT significantly decreased bleeding times in the sinonasal space compared to plain gauze (mean difference 5 3.8 minutes, P 5 .002). All of the carotid bleeds (100%) were successfully controlled with SPTT after 10 minutes of application under pressure, compared to 25% with Floseal. No adverse events were noted, and there was no evidence of thromboembolism. Conclusions: SPTT significantly reduced bleeding time in a sheep model of surgical sinus bleeding and successfully stopped bleeding following catastrophic carotid artery injury, with no adverse events observed.

To study the possibility of using thrombin generation tests in platelet-rich and platelet-poor plasma for evaluation of dual antiplatelet therapy efficacy in patients with coronary artery disease (CAD), following percutaneous coronary intervention. Venous blood was analyzed from CAD patients aged 53–75 years who had undergone percutaneous coronary intervention with
stenting within one year and had been receiving standard doses of clopidogrel and aspirin (75 and 75–100 mg per day, respectively). The control group comprised age- and sex-matched subjects without clinical signs of CAD who were not receiving these drugs. Thrombin generation tests were performed in platelet-rich and platelet-poor plasma. Intravascular platelet activation, induced platelet aggregation, and routine coagulation were evaluated.
Antiplatelet treatment did not influence results of routine coagulation tests or intravascular platelet activation. The dual antiplatelet therapy affects collagen-induced platelet aggregation (44 ± 2.5 vs. 7.9 ± 2.6%, р = 10−7) and leads to decreases in endogenous thrombin potential (1900 ± 85 vs. 1740 ± 95 nM∙min, p = 0.0045), maximum thrombin concentration (134 ± 9.5 vs. 106 ± 6.5 nM, p = 4∙10−6), and increases in time to peak thrombin (27 ± 1.5 vs. 31 ± 2 min, p = 0.0012). Decreases in thrombin generation rate showed the highest statistical significance (13 ± 2 vs. 7.9 ± 0.8 nM/min, p = 10−8). Antiplatelet treatment did not alter thrombogram parameters for platelet-poor plasma.

Abstract
INTRODUCTION:

Venous thromboembolism (VTE) is the third most common cardiovascular illness after acute coronary syndrome and stroke and and the most common preventable cause of hospital-related death. Several studies have demonstrated a significant reduction of fatal pulmonary embolism attributed to the introduction of thromboprophylactic measures and changes in hospital practices. However, the influence of some demographical variables, especially age, has largely been under appreciated.
METHODS:

Using the date of the TEVere study, we have studied 187 patients with VTE and 350 case-control, and we proceeded to analyze the major risk factors for venous thromboembolism, separately for three age groups (≤60 years, 60-75 years, >75 years). Patients came from the departments of internal medicine and emergency medicine for 21 hospitals. In this subgroup, we have examined the main risk factors for the individual classes of age and have proposed, through a logistic regression analysis, 3 different types of scores, specific for each age class. We then compared the individual scores obtained with the Kucher's score.
RESULTS:

It was found that in the class of patients with a lower age of 60, the main risk factors found to be estrogen-progestagen treatment (p=0.004) and family history of VTE (p=0.047), while in older patients (>75 years) the main risk factors were immobilization (p=0.005) and chronic venous insufficiency (p=0.001). In common for the three classes the presence of an evolutionary malignancy and previous episodes of VTE. Through the ROC curve analysis, it was found that the results for the three proposed scores improved sensitivity compared to Kucher's score. However our results showed that the only score of the intermediate class showed a statistically significant difference for prediction of the thromboembolic risk (p=0.0264 (AUROC 0.7946; 95% CI, 0.75 to 0.80, AUROC 0.7042; 95% CI, 0.68. to 0.72).
DISCUSSION:

Our study emphasizes the importance of carrying a correct stratification, which also consider the patient's age and therefore the concomitant pathologies. In fact, although the age of the patient cannot be considered as the only criterion to start the thromboprophylaxis, as highlighted in literature, you need to consider each individual patient, with its own peculiarities.
CONCLUSION:

This study showed the difficulty in identifying the key risk factors that are responsible for thromboembolic disease and has emerged the opportunity to be evaluated by larger studies, the use of specific scores by age groups

Defibrotide (DF), a polydeoxyribonucleotide with antithrombo-tic properties, has recently proven effective in patients with severe hepatic veno-occlusive disease (VOD), a life-threatening complication of high-dose chemo/radiotherapy regimens for stem cell transplantation. To understand the mechanism of its beneficial effect, we studied the impact of DF on the expression of tissue factor (TF) and fibrinolytic proteins (PAI-1 and t-PA) on endothelial cells. The in vitro response to DF of two types of human endothelial cells (ECs) of different origins, that is from macrovascular (HUVEC) and microvascular (HMEC-1 cell line) beds, was evaluated in the presence or absence of a proinflammatory stimulus (ie bacterial endotoxin, LPS). The results show that DF was able to significantly reduce the LPS-induced TF expression by HMEC-1, and less prominently by HUVEC. In addition, DF importantly influenced the fibrinolytic properties of both HMEC-1 and HUVEC. Specifically, it dose-dependently counteracted the LPS-induced increase in PAI-1 levels and decrease in t-PA activity expression. It also significantly incremented t-PA antigen in resting EC. Decreasing the procoagulant activity and increasing the fibrinolytic potential of EC favors an anticoagulant phenotype of the endothelium, which may protect from fibrin deposition and vascular occlusion.

Background: Hypothyroidism is an underactive thyroid gland that results in too little thyroid hormones in circulation causing a slowdown in metabolism, therefor hypothyroid modifies physiological process of primary and secondary hemostasis and may lead to a higher bleeding risk. Objectives: The aim of this study is to assess the coagulation profiles [Prothrombin Time (PT), International Normalize Ratio (INR), Activated Partial Thromboplastin Time (PTT)] in patients with hypothyroidism. Methodology: This is a case-control hospital-based study carried out at the National Cancer