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The cause of many myocardial infarctions is occlusive thrombosis, or a blood clot that stops blood flow in a coronary artery. Hemostasis involves a complex system of factors, which normally form and degrade blood clots, that work within a delicate balance. Emerging evidence suggests that some hemostatic factors, including factor VII, fibrinogen, and plasminogen activator inhibitor-1, are associated with increased risk for cardiovascular disease (CVD). Accumulating evidence suggests a relationship between dietary fatty acids and emerging hemostatic CVD risk factors, although much of this evidence is incomplete or conflicting. Dietary supplementation with marine n-3 fatty acids prolongs bleeding time and may decrease risk for thrombosis. Factor VII coagulant activity modestly decreases with reductions in saturated fatty acid (SFA) intake and thereby may contribute to the beneficial effects of low SFA diets. Large triglyceride-rich particles formed during postprandial lipemia can support the assembly and function of coagulation complexes and seem to play a role in the activation of factor VII, and thus may partially explain increased CVD risk associated with increased postprandial triglyceridemia. As our understanding of the role of dietary fatty acids and hemostasis evolves, it is likely that we will be able to make specific dietary recommendations to further decrease CVD risk. At this juncture, however, increasing marine n-3 fatty acids and decreasing certain SFAs are leading strategies to reduce hemostatic CVD risk factors. An array of dietary strategies that target multiple CVD risk factors could have a greater impact on CVD than a single risk factor intervention strategy.
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PMID:Dietary fatty acids, hemostasis, and cardiovascular disease risk. 1499 64

It has been suggested that fats rich in stearic acid may result in exaggerated postprandial lipemia and have adverse effects on hemostatic function. The effects of test meals containing different saturated and monounsaturated FA were compared in healthy subjects in a series of studies to investigate this hypothesis. Stearic acid, when present as cocoa butter, resulted in similar postprandial lipemia and factor VII activation compared with a meal containing high-oleic sunflower oil. Stearic acid when presented as shea butter or as randomized stearate-rich TAG resulted in decreased postprandial lipemia and decreased postprandial activation of factor VII. Stearic acid-rich test meals did not result in impaired fibrinolytic activity compared with either a low-fat meal or a meal high in oleate. The difference in responses between the different stearic acid-rich fats appears to be due to varying solid fat contents of the fats at 37 degrees C.
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PMID:Influence of stearic acid on postprandial lipemia and hemostatic function. 1647 6

Stearic acid has been claimed to be prothrombotic. Elevated plasma factor VII coagulant activity (FVIIc) may raise the risk of coronary thrombosis in the event of plaque rupture. Fibrinogen, an acute-phase protein, is necessary for normal blood clotting; however, elevated levels of fibrinogen increase the risk of coronary heart disease (CHD). Here I report the results of three controlled, human dietary intervention studies, which used a randomized crossover design to investigate the hemostatic effects of stearic acid-rich test diets in healthy young men. A diet high in stearic acid (shea butter) resulted in a 13% lower fasting plasma FVIIc than a high palmitic acid diet, and was 18% lower than a diet high in myristic and lauric acids (P = 0.001) after 3 wk of intervention. The stearic acid-rich test fat increased plasma fibrinogen concentrations slightly compared with the myristic-lauric acid diet (P < 0.01). When investigating the acute effects of fatty meals, those high in stearic acid (synthesized test fat) resulted in a smaller postprandial increase in FVII than those high in trans and oleic FA, indicating a smaller increase in activated FVII after ingesting stearic acid compared with fats high in monounsaturated FA, probably caused by lower postprandial lipemia. Thus, the present investigations did not find dietary stearic acid to be more thrombogenic, in either fasting effects compared with other long-chain FA, or in acute effects compared with dietary unsaturated FA, including trans monounsaturated FA. The slightly increased effect on fasting plasma fibrinogen may be biologically insignificant, but it should be investigated further.
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PMID:Influence of stearic acid on hemostatic risk factors in humans. 1647 7

Chronic hypertriglyceridemia is thought to be atherogenic and is associated with an elevated thrombotic potential, both of which may be improved with aerobic exercise training. Eight subjects were tested for aerobic capacity, body composition, and postprandial lipemia (PPL), followed by 6 mo of exercise training and final testing. Blood samples were obtained for measurement of free fatty acid (FFA), triglycerides (TG), insulin (Ins), and glucose (Glu). Hemostatic variables including factor VII activity (FVIIa), tissue factor pathway inhibitor-factor Xa complex (TFPI/Xa), and plasminogen activator inhibitor-1 (PAI-1) antigen/activity as well as leukocyte tumor necrosis factor-alpha (TNF-alpha) gene expression were determined among four subjects. We found that the exercise training was of sufficient intensity to increase aerobic capacity (P < 0.0001) and improve body composition (P = 0.04). There were no differences between tests among PPL responses of FFA, TG, Ins, or Glu; however, the mean TG response and fat oxidation rate improved. PAI-1 antigen/activity, FVIIa, TFPI/Xa, and TNF-alpha gene expression were all improved after exercise training after adjusting for confounders. We conclude that aerobic exercise training reduces the potential for coagulation, improves fibrinolytic potential, and reduces leukocyte TNF-alpha gene expression after the ingestion of a high-fat meal.
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PMID:Hemostatic response to postprandial lipemia before and after exercise training. 1649 41

A 66-year-old man with hypertension and hyperlipidemia developed a hemorrhagic stomal ulcer and massive hematoma of the face at 4 and 7 months, respectively, after fundusectomy for early gastric cancer. The diagnosis of acquired hemophilia A was made based on the marked prolongation of activated partial thromboplastin time, an extremely low factor VIII activity, and a very high-titer factor VIII inhibitor. After admission, oral prednisolone and cyclophosphamide were started. In addition, activated prothrombin complex concentrates and recombinant activated factor VII were intravenously administered which successfully controlled his hemorrhage. Only 1 week after the episode of bleeding, however, he complained of abdominal pain accompanied by watery stool with fresh blood. The diagnosis of ischemic colitis was made based on the clinical course and the findings on both CT-scan and colon fiberoscopy. The colitis spontaneously and quickly resolved with conservative observation. To the best of our knowledge, this is the first reported case of ischemic colitis that occurred in an acquired hemophilia patient without simultaneous administration of coagulation factors or antifibrinolytic agents. We should thus pay attention to the possible occurrence of thrombotic events even in acquired hemophilia patients in the presence of risk factors for thrombosis.
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PMID:[Ischemic colitis following the treatment of acute hemorrhage in a patient with acquired hemophilia A]. 1671 66

The process of interesterification results in changes in triacylglycerol (TAG) structure and is used to increase the melting point of dietary fats. The acute health effects of this process on palmitic acid-rich fats are uncertain with regard to postprandial lipemia, insulin and factor VII activated (FVIIa) concentrations. Two randomized crossover trials in healthy male subjects compared the effects of meals containing 50 g fat [interesterified palm oil (IPO) versus native palm oil (NPO); n=20, and IPO versus high-oleic sunflower oil (HOS); n=18], on postprandial changes in lipids, glucose, insulin, chylomicron composition and FVIIa. Compared with NPO, IPO decreased postprandial TAG and insulin concentrations. Both NPO and IPO increased FVIIa concentrations postprandially; mean increases at 6 h were 21 and 19%, respectively. Compared with HOS, IPO decreased postprandial TAG (47% lower incremental area under the curve) and reduced the postprandial increase in FVIIa concentration by 64% at 6 h; no significant differences in hepatic and total lipase activities or insulin concentrations were noted. All three test meals increased postprandial leukocyte counts (average 26% at 6 h). The fatty acid composition of the chylomicron TAG was similar to the test fats following all test meals. It is concluded that interesterification of palm oil does not result in adverse changes in postprandial lipids, insulin or FVIIa compared to high oleate and native palm oils.
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PMID:Effect of interesterification of palmitic acid-rich triacylglycerol on postprandial lipid and factor VII response. 1740 26

Subclinical hypothyroidism (SH) is a frequent condition affecting millions of people around the world. Defined by increased thyrotropin-stimulating hormone (TSH) and accompanied by normal thyroid hormone levels, SH reflects a mild tissue hypothyroidism that has been associated with metabolic derangements and-although this issue is still contentious-possibly with increased cardiovascular risk. Depending on the degree of TSH elevation, SH has accordingly been associated with hyperlipidemia, arterial hypertension, and cardiovascular disease (CVD), as well as, increasingly, newly emerging CVD risk factors such as serum C-reactive protein and retinol binding protein 4 levels. There have also been reports of abnormalities in glucose metabolism and of hemostatic parameters, mainly underscored by the increased activity of factor VII. This review discusses the results of the latest studies on the various parameters affected by SH while highlighting the need for timely treatment with levothyroxine.
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PMID:New insights into subclinical hypothyroidism and cardiovascular risk. 2124 2

Hemophilia is a bleeding diathesis that is most commonly congenital and causes a tendency for significant bleeding during procedures and often manifests as hemarthrosis. However, more rarely, hemophilia can be acquired. Our paper focuses on acquired hemophilia A (AHA), which is caused by the development of an autoantibody (an inhibitor) to factor VIII. A 61-year-old man with a past medical history of type II diabetes mellitus, hypertension, hyperlipidemia, hypothyroidism, and obstructive sleep apnea presented to the emergency department with severe right lower extremity pain and swelling of 2-day duration. He was found to have compartment syndrome and underwent emergent fasciotomy of his right leg. After surgery he still had significant bleeding, despite transfusions and administration of fresh frozen plasma (FFP) by the surgical team. He was later diagnosed with AHA, but was not adequately responsive to factor VII, factor VIII, steroids nor rituxan and unfortunately had his right lower extremity amputated. He had a prolonged hospital course, which included Streptococcus bovis bacteremia and a code stroke for which head computed tomography (CT) showed probable metastasis. It was acknowledged he had probable metastatic colon cancer, which was not confirmed as the patient transitioned to hospice care. Rather than hemarthrosis, patients with AHA tend to have bleeding in soft tissue or the gastrointestinal tract. AHA can have underlying causes, such as malignancy. AHA associated with malignancy is associated with poorer outcomes and tends to improve with treatment of the underlying malignancy. Therefore, it is important to quickly identify these patients and screen them for underlying etiologies.
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PMID:A Unique Presentation of Spontaneous Compartment Syndrome due to Acquired Hemophilia A and Associated Malignancy: Case Report and Literature Review. 3228 75


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