Abnormal sialic acid content of the dysfibrinogenemia associated with liver disease.

Martinez, Josè; Palascak, Joseph E.; Kwasniak, D

doi:10.1172/jci108964

Cited by 111 publications

(40 citation statements)

References 13 publications

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“…However, moderate prolongation of both TT and reptilase time was common and suggests a possible dysfibrinogenemia. Abnormal fibrin polymerization is known to occur in liver disease (16) and is reported to be related to an excessive sialic acid content in the fibrinogen molecule (17,18). The clinical significance of the acquired dysfibrinogenemia in patients with liver disease and its role in patients undergoing liver transplantation requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Intraoperative Changes in Blood Coagulation and Thrombelastographic Monitoring in Liver Transplantation

Kang

Martin

Marquez

et al. 1985

Anesthesia & Analgesia

623

432

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The blood coagulation system of 66 consecutive patients undergoing consecutive liver transplantations was monitored by thrombelastograph and analytic coagulation profile. A poor preoperative coagulation state, decrease in levels of coagulation factors, progressive fibrinolysis, and whole blood clot lysis were observed during the preanhepatic and anhepatic stages of surgery. A further general decrease in coagulation factors and platelets, activation of fibrinolysis, and abrupt decrease in levels of factors V and VIII occurred before and with reperfusion of the homograft. Recovery of blood coagulability began 30-60 min after reperfusion of the graft liver, and coagulability had returned toward baseline values 2 hr after reperfusion. A positive correlation was shown between the variables of thrombelastography and those of the coagulation profile. Thrombelastography was shown to be a reliable and rapid monitoring system. Its use was associated with a 33% reduction of blood and fluid infusion volume, whereas blood coagulability was maintained without an increase in the number of blood product donors. Keywords BLOOD-coagulation; LIVER-transplantationLiver transplantation, which began as highly experimental surgery 20 yr ago, is now recognized as a major means of therapy for patients with end-stage liver disease (1). However, massive blood loss during liver transplantation is still a major concern. The liver produces most of the blood coagulation factors, so it is not surprising that we see very low levels of these factors and prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) in many patients receiving liver transplants (2). Frequently we have seen thrombocytopenia, which may result from gastrointestinal bleeding, splenomegaly, or malnutrition (3). At the same time, numerous collateral channels and portal hypertension, together with increased capillary fragility, make maintenance of surgical hemostasis very difficult.Previous studies on the blood coagulation system in humans and in animals undergoing liver transplantation have demonstrated dilutional coagulopathy associated with massive blood transfusion, decreased fibrinogen levels, and thrombocytopenia (4,5). Fibrinolysis, beginning during the anhepatic stage of surgery and becoming "explosive" on reperfusion of the homograft, has been reported (6). A consumption coagulopathy accompanied by an increased level of fibrin degradation products appeared to play a major role (7). However, these observations were limited to a few patients in the early era of liver transplantation, and comprehensive information is still lacking.Another difficulty in the intraoperative management of liver transplantation has been actively monitoring the coagulation system and determining the appropriate treatment during dynamic blood volume changes. The use of the thrombelastograph (TEG) was suggested by von Kaulla et al. (4) and Howland et al. (8). However, the efficacy of thrombelastographic monitoring of blood coagulation during liver transplantatio...

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Section: Discussionmentioning

confidence: 99%

Intraoperative Changes in Blood Coagulation and Thrombelastographic Monitoring in Liver Transplantation

Kang

Martin

Marquez

et al. 1985

Anesthesia & Analgesia

623

432

View full text Add to dashboard Cite

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“…For example, in patients with severe liver disease there is excess sialylation of fibrinogen on the y-chains, and this renders it a less efficient substrate for thrombin, consequently prolonging the thrombin time (23).…”

Section: Discussionmentioning

confidence: 99%

An abnormal triglyceride-rich lipoprotein containing excess sialylated apolipoprotein C-III.

Holdsworth¹,

Stocks²,

Dodson³

et al. 1982

J. Clin. Invest.

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AB S T R A C T An abnormal triglyceride-rich lipoprotein has been isolated from some patients with chronic renal failure or severe hypertriglyceridemia. The abnormal lipoprotein was characterized by an increased content of apolipoprotein (apo) C-III-2 (57.5% of total apo C-III peptides compared with 35.5% for controls, P < 0.001) as characterized by isoelectric focusing and scanning densitometry. As determined by a substrate competition assay, the abnormal lipoprotein was a less efficient substrate for purified bovine milk lipoprotein lipase than control lipoproteins. Neuraminidase digestion of abnormal or control lipoprotein resulted in a reduction of the apo C-III-2 band with a corresponding increase in the region of apo C-III-0, which suggests that the increased content of apo C-III-2 in the abnormal is due to excessive sialylation of the C-III peptide. Limited incubation of the abnormal lipoproteins with neuraminidase caused a partial loss of sialic acid and resulted in a triglyceride-rich lipoprotein with a normal C-III-2:C-III-1 ratio. This preparation displayed normal substrate interaction with lipoprotein lipase. Three severely hypertriglyceridemic patients with the abnormal lipoprotein showed a marked reduction in serum triglyceride concentration, which is associated with a reversion to a normal C-peptide profile after dietary therapy. The results suggest that the extent of sialylation of the apo C-III peptide carried on triglyceride-rich lipoproteins may be critical for their interaction with lipoprotein lipase.

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“…In contrast, increased sialic acid in liver disease is associated with dysfibrinogenemia and abnormal fibrin polymerization. Increased blood clotting time is directly correlated with increasing sialic acid content of fibrinogen and removal of sialic acid from patient's platelets normalizes blood clotting times [Martinez et al, 1978].…”

Section: Blood-related and Vascular Disordersmentioning

confidence: 99%

Glycoproteins and Their Relationship to Human Disease

Brockhausen

Schutzbach

Kuhns

1998

Cells Tissues Organs

167

105

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Glycoproteins are proteins that carry N- and O-glycosidically-linked carbohydrate chains of complex structures and functions. N-glycan chains are assembled in the endoplasmic reticulum and the Golgi by a controlled sequence of glycosyltransferase and glycosidase processing reactions involving dolichol intermediates. The assembly of O-glycans occurs in the Golgi and does not involve dolichol. For most reactions, families of glycosyltransferases exist; the expression of the individual enzymes within a family is often subject to complex regulation. The biosynthesis of N- and O-glycan is controlled at the level of gene expression, mRNA, enzyme protein activity and localization, and through substrate and cofactor concentrations at the site of synthesis. This complex regulation results in many hundreds of structures, the range of which varies in different species, cell types, tissue types, states of development and differentiation. In diseased cells, the relative proportions of these structures are often characteristically different from normal, and may be useful for the assessment of the stage of the disease and for diagnosis. Knowledge of disease-specific glycoprotein structures and their functions may be used therapeutically, in immunotherapy, in blocking cell adhesion or interfering with other binding or biological processes. Recently, some of the mechanisms underlying glycoprotein alterations in disease have been elucidated. This opens the possibility of an active interference in the disease process. The functions of glycans in diseased cells will become more clear with the tools of molecular biology and transgenic animal models.

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Abnormal sialic acid content of the dysfibrinogenemia associated with liver disease.

Cited by 111 publications

References 13 publications

Intraoperative Changes in Blood Coagulation and Thrombelastographic Monitoring in Liver Transplantation

Intraoperative Changes in Blood Coagulation and Thrombelastographic Monitoring in Liver Transplantation

An abnormal triglyceride-rich lipoprotein containing excess sialylated apolipoprotein C-III.

Glycoproteins and Their Relationship to Human Disease

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