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Biomedical subjects

A Ordinas

Publications and source records attributed to A Ordinas.

At least 109 records · Page 6Linked to original sources
PubMed1995

Reticulated platelets in uremic patients: effect of hemodialysis and continuous ambulatory peritoneal dialysis.

Platelet RNA content can be detected by flow cytometry using thiazole orange staining to identify platelets recently released into the circulation. We studied platelet RNA content and platelet function in uremic patients under different treatment regimens. Four groups were studied: (I) 15 end-stage renal disease (ESRD) patients (10M/5F) on maintenance hemodialysis (HD); (II) 11 ESRD patients (6M/5F) on continuous ambulatory peritoneal dialysis (CAPD); (III) 8 patients with chronic renal failure managed conservatively (5M/3F); and (IV) 34 controls (20M/14F). A double color labeling technique using a phycoerythrin-tagged antibody against glycoprotein Ib (CD42b) and RNA labeling by thiazole orange was performed and read by flow cytometry. Aggregation studies were made in platelet-rich plasma using ADP, epinephrine, collagen, arachidonic acid, and ristocetin. In group I, samples were also obtained after HD. Platelet counts did not differ among the groups. Aggregation studies showed a lower response to ADP and ristocetin in the HD patients, but not in the CAPD or in the chronic renal failure patients. The percentage of platelets with high RNA content in group I was significantly lower than in controls (3.72 +/- 1.72% vs. 9.05 +/- 3.53%, P < 0.01), but was also lower than in the remaining groups (I vs. II P < 0.01, and I vs. III P < 0.01). No differences were seen in platelet RNA content among groups II (8.67 +/- 2.73%), III (9.14 +/- 3.04%) and IV. In group I, the percentage of reticulated platelets decreased further after HD (2.14 +/- 1.09%, P < 0.01). Aggregation studies showed a significantly lower response to ADP and ristocetin in group I (P < 0.05), but not in groups II or III in comparison with controls. Aggregation response to ADP and ristocetin decreased after HD (P < 0.05). In conclusion, HD may decrease the percentage of RNA-rich platelets through elimination of the younger and more active platelets and worsen the thrombopathy present in uremic patients.

Adult↗
PubMed1995

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a multivariate analysis of factors predicting the response to plasma exchange.

The aim of this study was to investigate pretreatment prognostic factors that could be useful in predicting the response to plasma exchange in thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Thirty-two patients with TTP/HUS, treated with plasma exchange at our institution from 1980 to 1994, were studied. The main clinical and laboratory data at the beginning of plasma exchanges were analyzed by the Cox stepwise logistic regression, applied to either treatment failure or death. Seventeen (53%) patients attained a complete remission and 22 (69%) survived (five in advanced renal failure and long-term hemodialysis). Longer delay in initiating plasma exchanges, presence of stupor or coma, and higher creatinine levels at the beginning of plasma exchanges were independent predictors of treatment failure. Stupor or coma at the beginning of plasma exchanges was the only predictor of mortality from unremitted TTP/HUS. Hemoglobin levels, platelet count, and LDH activity, traditionally envisaged as markers of disease activity, neither correlated with previous duration of TTP/HUS nor had any prognostic value. Early diagnosis of TTP/HUS and prompt initiation of intensive plasma exchange emerged from this study as the most effective interventions for improving the prognosis of TTP/HUS patients.

Adolescent↗
PubMed1995

Platelet concentrates promote procoagulant activity: evidence from experimental studies using a perfusion technique.

BACKGROUND: Evaluation of the hemostatic effectiveness of platelet transfusions is difficult. Perfusion methods have been employed to test the quality and function of platelet concentrates, allowing differentiation between platelet-platelet and platelet-surface interactions. STUDY DESIGN AND METHODS: A study was performed to investigate platelet adhesive and cohesive properties as well as the formation of fibrin when aliquots of platelet concentrates were added to thrombocytopenic blood. Blood previously anticoagulated with low-molecular-weight heparin (20 U/mL) underwent platelet and white cell reduction by filtration. Perfusates were prepared by adding to filtered blood platelets obtained from standard concentrates (stored for 1, 3, and 5 days). The final platelet count in these perfusates was standardized at 80,000 per microL. After perfusions, platelet-subendothelium interaction and fibrin formation were analyzed morphometrically. Results were always compared with those obtained in unfiltered blood (> 150,000 platelets/microL). RESULTS: A slight impairment in the ability of stored platelets to interact with the subendothelium was noticed during the storage period. However, the presence of fibrin was significantly greater than that observed in studies with unfiltered blood (Day 1 = 23.48 +/- 9.43%*; Day 3 = 26.99 +/- 6.74%*; Day 5 = 17.95 +/- 9.06% vs. unfiltered blood = 12.60 +/- 3.08%; *p < 0.05). The lower platelet counts (80,000/microL) in the perfusates containing platelets from concentrates could account for the reduced platelet-subendothelium interactions, but they cannot explain the increments in fibrin formation. CONCLUSION: While the preparation and storage of platelets have a detrimental effect on platelet adhesiveness, such procedures can positively influence the platelet procoagulant activity necessary to platelet hemostasis.

Animals↗
PubMed1995

Uraemic medium causes endothelial cell dysfunction characterized by an alteration of the properties of its subendothelial matrix.

Uraemic patients suffer from haemorrhagic disorders and accelerated atherosclerosis. To evaluate the possible role of the vessel wall in these haemostatic alterations associated with uraemia, we investigated the effect of a uraemic milieu on human endothelial cell (EC) cultures and the reactivity of the extracellular matrices (ECM) generated by these cells towards platelets. EC cultures were exposed to a pool of sera (20% in the culture medium) obtained either from uraemic patients or from normal donors, and the following parameters were evaluated: (1) EC viability (trypan blue exclusion test); (2) von Willebrand factor (vWF) levels in supernatants and associated with ECM; (3) the reactivity of EC and EC-derived ECM towards platelets, measured 'ex vivo' under flow conditions (5 min, wall shear rate 800 s-1); and (4) ultrastructure of the ECM. The viability of EC cultured in the presence of uraemic sera was similar to controls. Platelet interaction with ECM generated by EC exposed to uraemic sera was significantly reduced (P < 0.05). This decrease was mainly related to a reduction in platelet adhesion (9.8 +/- 1.9% vs 16.7 +/- 1.8% in controls, P < 0.02). VWF levels in supernatants and associated with ECM were similar to controls. Ultrastructural analysis of the ECM generated by EC exposed to uraemic sera revealed a deficient matrix. An increased removal of EC was observed in experiments in which EC cultured in the presence of uraemic sera were perfused with citrated blood. These results indicate that a uraemic milieu induces quantitative and qualitative changes in the vascular subendothelium, characterized by a less intrincate network of fibrils, as well as a decreased attachment of EC and reduced thrombogenicity to the ECM. These changes may represent another mechanism which contributes to the haemostatic dysfunction observed in uraemic patients.

Blood Platelets↗
PubMed1995

Persistent hepatitis C viremia after acute self-limiting posttransfusion hepatitis C.

Persistent viremia after clinical or subclinical hepatitis C virus (HCV) infection is believed to occur in patients with chronic hepatitis C, but little is known about the duration of HCV replication in patients with acute hepatitis who have recovered or the relation of HCV viremia with the kinetics of antibodies to HCV (anti-HCV). We tested HCV-RNA and anti-HCV in serial serum samples from 41 patients with posttransfusion non-A, non-B hepatitis, followed for an average of 6 years after transfusion. Serum HCV-RNA was measured by nested polymerase chain reaction, which used primers from the 5' untranslated region of the HCV genome. Anti-HCV were tested with first- and second-generation enzyme-linked immunosorbent assays (ELISA 1 and ELISA 2), and with a second-generation recombinant immunoblot assay. Of the 41 patients, 10 recovered and 31 progressed to chronic liver disease. HCV-RNA was detected in serum before or simultaneously with the onset of hepatitis in all cases, and lasted between 2 and 6 weeks in 5 of the 10 patients who recovered, whereas it persisted for the entire follow-up period in every case with chronic hepatitis and in the remaining 5 patients with self-limiting hepatitis. Anti-HCV were detected with ELISA 2 in the first serum sample, with raised serum transaminases in 57% of patients, but in only 6% with ELISA 1. In the sample obtained 1 month after the onset of hepatitis, anti-HCV were detected with ELISA 2 in 94% of patients, but in 34% with the ELISA 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effect of plasma from patients with primary antiphospholipid syndrome on platelet function in a collagen rich perfusion system.

The effect on platelet function of plasma from 9 patients with primary antiphospholipid syndrome (PAS) with previous thrombotic episodes was investigated under flow conditions. Five asymptomatic individuals with antiphospholipid antibodies (aPL) (A-aPL) and 14 normal controls were also studied. Patients and controls plasmas were added (1:20 v/v) to anticoagulated blood and perfused through annular chambers containing collagen rich vessel segments. The interaction of platelets with vessel subendothelium was morphometrically evaluated in thin sections. An increase in both covered surface and thrombi formation was observed in perfusions in the presence of PAS-plasma (mean +/- SD: 34.2% +/- 9.6% and 23.2% +/- 10.0% respectively) compared with control plasmas (21.4% +/- 7.3% and 10.1% +/- 7.7%, p < 0.01). Affinity purified anticardiolipin antibodies from one PAS patient showed a similar effect when added to normal blood. In contrast, A-aPL plasma had no effect on platelet-subendothelium interaction. In parallel studies, the same plasmas were incubated with isolated normal platelets before and after activation with ADP or collagen and the binding of immunoglobulins (Ig) was determined by flow cytometry. A significantly increased binding of Ig was observed in 8 out of 9 plasmas from PAS patients when platelets had been activated with collagen but not when resting or ADP activated platelets were used. No increased Ig binding to platelets was seen using A-aPL individuals plasma. These observations might help to explain the pathophysiology of the thrombotic events occurring in patients with PAS.

Adult↗
PubMed1995

[Expression of von Willebrand's disease in endothelial cord cell from a type 1 patient. Discrepancies between clinical manifestations and laboratory tests].

PURPOSE: The reactivity of subendothelium generated by endothelial cells attained from the umbilical cord of a newborn girl from a patient with type I von Willebrand's disease was evaluated. MATERIAL AND METHODS: Platelet adhesiveness was assessed by means of "ex vivo" blood perfusion systems (shearing coefficients from 300 to 1,300 s-1), on umbilical artery subendothelium and over the extracellular matrix (ECM) generated by cultured endothelial cells attained from the umbilical cord of a newborn baby from a type I von Willebrand mother. RESULTS: By means of an ELISA technique, a significant reduction of both the vWF secreted into the culture (p < 0.05) and of that associated with ECM (p < 0.05) was noticed. The two subendothelial surfaces examined supported a lesser extent of platelet adhesion than the control surfaces from healthy individuals in the perfusion tests at 1,300 s-1 (p < 0.05). The experimental results did not agree with the lack of clinical manifestations and laboratory abnormalities in the propositus at age 3. CONCLUSIONS: These findings suggest that the endothelial cells cultured from the tissues of a newborn baby from a type I von Willebrand woman expressed less vWF, at the same time confirming the importance of vWF bound to connective tissue in sustaining platelet adhesion. The data attained here illustrate the complex model of inheritance of moderate von Willebrand's disease, along with the technical limitations of cell culture studies. Such observations must be borne in mind whenever any experimental approach is performed with material attained from ill-differentiated tissues such as the umbilical cord vein.

Endothelium, Vascular↗
PubMed1995

Reduced red cell deformability associated with blood flow and platelet activation: improved by dipyridamole alone or combined with aspirin.

OBJECTIVES: To explore the role of blood flow in red blood cell deformability and determine whether it is associated with the release of ATP by red cells. METHODS: A perfusion system was employed to mimic the blood flow conditions. Red cell treatment in vitro with dipyridamole or aspirin, either alone or combined, was performed either on red cells alone prior to blood reconstitution or on already reconstituted blood. Blood viscosity at shear rates of 90 and 450 s-1 was measured, before and after perfusion, by means of a cone/plate viscometer. Red cell deformability was estimated as the magnitude of the slope between these two values of viscosity. ATP level in platelet-free plasma was measured by the firefly luciferase assay, and was used to monitor dipyridamole-induced blockade of ATP efflux by red cells. RESULTS: In control experiments, red cells became more rigid after perfusion (slope values: 0.62 +/- 0.09 vs 0.40 +/- 0.04; P < 0.05). Absence of platelets or treatment of red cells with aspirin and/or dipyridamole prevented dipyridamole prevented the increased stiffness of red cells observed after exposure of blood to flow conditions. Moreover, a significant increase in red cell deformability was observed when blood was treated with dipyridamole alone or combined with aspirin (0.69 +/- 0.07 and 0.65 +/- 0.05 respectively vs. 0.40 +/- 0.04; P < 0.05). Treatment with dipyridamole alone or combined with aspirin caused a decrease in ATP levels. Statistical significance was reached when red cells alone were treated with dipyridamole alone (45.8 +/- 2.8 vs. 173.3 +/- 47.6 ng ATP/ml; P < 0.05). CONCLUSIONS: Flow stress induced a decrease in red cell deformability probably linked to platelet activation. Treatment with dipyridamole alone or associated with aspirin eliminated the effect of flow, increasing red cell deformability. Under our experimental conditions, modifications could not be ascribed to red cell-released ATP. Our results emphasize the importance of blood flow conditions to evaluate RBC deformability.

Adenosine Triphosphate↗
PubMed1994

Two human antibodies reacting with different epitopes on integrin beta 3 of platelets and endothelial cells.

Glanzmann's thrombasthenia is an inherited bleeding disorder that results from a deficit of glycoprotein (GP) IIb-IIIa complexes in platelets. Patient (EBV) is an adult male with GP IIb-IIIa levels < 5% of normal values and a history of blood transfusions. Western-blot analysis revealed a strong IgG antibody to GP IIIa in his plasma. The determinants were localized to the minimum-sized fragment of GP IIIa (50 kDa) retained on chymotrypsin-treated platelets and were lost on reduction of disulphides. A female patient (AF), previously described by us [Jallu, V., Pico, M., Chevaleyre, J., Vezon, G., Kunicki, T.J. & Nurden, A.T. (1992) Hum. Antibod. Hybridomas 3, 93-106] developed her anti-GP-IIIa antibody during pregnancy. This antibody was poorly reactive with the 50-kDa proteolytic fragment, yet bound to 115-kDa and 60-kDa hydrolytic products of GP IIIa. Antibodies from both patients recognized the GP-IIIa-like protein of endothelial cells, thus confirming that they were directed against the integrin beta 3-subunit. The (EBV) antibody reacted strongly with GP IIb-IIIa in an antigen capture assay performed with each of a panel of four murine monoclonal antibodies (mAbs) recognizing different epitopes on GP IIb-IIIa. In contrast, that from (AF) was specifically inhibited by AP-3, a murine mAb whose epitope is thought to be localized between amino acids 324-422 of GP IIIa. The residual GP IIb and GP IIIa contents of platelets from each patient were assessed in Western blotting using chemiluminescence detection. SZ-22, a murine mAb to the GP IIb heavy chain (140 kDa), located small amounts of a 130-kDa protein in (EBV) platelets. The anti-GP IIIa mAbs XII F9, P 37 and P 97 revealed trace amounts of protein with a relative mobility identical to that of GP IIIa in both (AF) and (EBV) platelets. This residual GP IIIa represented less than 0.5% of the amount in normal platelets. When, for each patient, plasma was tested in Western blotting against their own platelets, autoantibody activity to the residual GP IIIa was detected in both cases. Thus, patients (AF) and (EBV) have developed anti-GP-IIIa antibodies with restricted and distinct epitopes but recognizing self antigens.

Antigen-Antibody Reactions↗
PubMed1994

Influence of co-incubation and cell number of platelets and polymorphonuclear leukocytes in cellular inhibition and activation phenomena.

Evidence indicates that complex interactions occur between blood platelets and polymorphonuclear leukocytes (PMN) referring to both activation and inhibition phenomena. We studied the influence of co-incubating activated PMN and platelets at varying cell counts in the production of two active metabolites, thromboxane A2 (TxA2) measured as thromboxane B2 (TxB2) and platelet activating factor (PAF). The decrease observed in the quantity of TxA2 synthesized by 2 x 10(8) platelets/ml in the presence of physiological PMN counts clearly indicates an inhibitory effect of PMN in AA-derived metabolites. This suggests there is an influence of PMN-released products on activated platelets, decreasing their capacity to synthesize TxA2. Moreover, we found that the addition of platelets, which do not make measurable quantities of PAF, to PMN suspensions significantly decreased the capacity of PMN to synthesize this mediator. Together with this inhibiting action we also observed an activating effect, in such a way that the more PMN were added to platelet suspensions the more TxA2 was produced. Conversely, the maximal amounts of PAF were synthesized when the highest platelet count suspensions were added to PMN. In summary, the results we present here clearly show cellular interactions between platelets and PMN that directly influence the amounts of metabolites synthesized by both cells.

Blood Platelets↗
PubMed1994

Suitability of low-molecular-weight heparin(oid)s and a pentasaccharide for an in vitro human thrombosis model.

There is much interest in in vitro thrombosis systems using exclusively human materials for evaluating new drugs. We have previously developed such a model using a perfusion chamber in which whole blood anticoagulated with low-molecular-weight heparin (LMWH) was circulated over the extracellular matrix of endothelial cells that had been stimulated with phorbol myristate acetate to cause tissue factor formation. Here we studied various LMWHs and a pentasaccharide to find out which was most useful in an in vitro thrombosis model. We compared unfractionated heparin, two commercial LMWHs (Fragmin and Fraxiparine), one commercial heparinoid (Orgaran), and a chemically synthesized derivative of the natural pentasaccharide (Org 31550). Blood was anticoagulated with the concentration of each glycosaminoglycan that prevented thrombin formation for at least 3 hours in the test tube (Fragmin, 20 anti-Xa U/mL; Fraxiparine, 40 anti-Xa Institute Choay U/mL; Orgaran, 15 anti-Xa U/mL; Org 31550, 200 anti-Xa U/mL; unfractionated heparin, 5 IU/mL) and recirculated over the matrix of unstimulated cells (no tissue factor in the matrix) and phorbol-stimulated endothelial cells (tissue factor in the matrix). Platelet adhesion, aggregate formation, and fibrin deposition were evaluated. In perfusions over the extracellular matrix of unstimulated cells, the highest platelet adhesion rates were observed with Orgaran. Fibrin deposition was absent with unfractionated heparin in phorbol-stimulated matrix. Increasing amounts of fibrin were observed with Orgaran, Fragmin, and Fraxiparine. Most fibrin was found with the pentasaccharide Org 31550.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗
PubMed1994

Platelet activation during hemodialysis measured through exposure of p-selectin: analysis by flow cytometric and ultrastructural techniques.

P-selectin is a platelet protein in alpha-granules that is expressed on their membranes after platelet activation. Using a specific monoclonal antibody (RUU-2.17), we have studied platelet activation during hemodialysis with a cuprophan membrane in eight patients with uremia. Blood samples were obtained before hemodialysis from venipuncture (sample I), at the beginning of the hemodialysis from the arterial (sample II) and venous lines (sample III), and after 2 hours of hemodialysis from the venous line (sample IV). Exposure of P-selectin on platelet surface was studied by flow cytometry, and morphologic and immunocytochemical studies were performed. No differences in P-selectin expression were observed by single-labeling flow cytometry in samples I, II, and IV. However, a significant increase in fluorescence occurred in sample III (percentage of positive platelets [%PP], 18.0% +/- 6.1%) with respect to sample I (%PP, 6.9% +/- 2.0%; p < 0.01). An apparently decreased fluorescence was seen in sample IV (%PP, 8.8% +/- 3.9%) with respect to sample III. Double-labeling flow cytometry showed statistically significant differences between sample I (%PP, 7.1% +/- 2.6%) and sample III (%PP, 19.4% +/- 9.4%; p < 0.01) and IV (%PP, 19.0% +/- 10.1%; p < 0.01), but not between samples III and IV. The ultrastructural study revealed an increasing number of platelet morphologic signs of activation throughout the period of hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Interaction of platelets with an artificial polystyrene surface under flow conditions: comparative study versus collagen].

PURPOSE: Platelets are known to interact with artificial surfaces, which leads to thrombosis that in turn may hamper repairing surgery. In order to evaluate such interaction, platelet adhesiveness on a polystyrene surface (Thermanox) was studied in an in vitro perfusion model. MATERIAL AND METHODS: Anticoagulated human blood was recirculated through a plain perfusion chamber containing fragments of the material under study, uncovered and covered with collagen. The studies were performed at a shearing coefficiente of 800 s-1 and with different timing. Additional blood samples were incubated with an anti- GPIIb-IIIa antibody. Platelet deposition on the perfused material was morphometrically evaluated with a computerized system of image analysis. RESULTS: The values attained, expressed as percent surface covered by platelets over the uncovered polystyrene surface, at 2, 5, 10 and 20 minutes, were, respectively, as follows: 10.4% +/- 1.83%, 27.04% +/- 2.32%, 36.04% +/- 3.09% and 61.48% +/- 8.86%; for the collagen-covered material these figures were: 35.2% +/- 1.3%, 47.8% +/- 4.2%, 71.7% +/- 2.4% and 73% +/- 3.2%, for similar timing (n = 7 for each group). CONCLUSIONS: The perfusion method proved useful for evaluating the interaction of platelets with artificial surfaces. These data show their polystyrene surfaces have high reactivity toward platelets and confirm that GPIIb-IIIa plays an important role in this reactivity.

Blood Platelets↗
PubMed1993

Platelets lacking functional CD36 (glycoprotein IV) show reduced adhesion to collagen in flowing whole blood.

A parallel-plate perfusion chamber has been used to evaluate the contribution of the adhesive membrane glycoprotein CD36 (GPIV) to platelet adhesion on type I collagen in flowing whole blood at a shear rate of 800 s-1. In one series of experiments, reconstituted normal blood (hematocrit 0.4; platelet count 1.5 x 10(5)/microL) was prepared from washed red blood cells, plasma, and washed platelets that had been incubated with Fab fragments of a monospecific polyclonal anti-CD36 antibody (50 micrograms/mL, 30 minutes, 37 degrees C). Percent surface coverage of collagen-coated coverslips using reconstituted blood with antibody-blocked platelets, as compared with paired reconstituted controls (100%), was 50% at 2 minutes, 87% at 5 minutes, and 90% at 10 minutes. Further studies were performed by perfusion of whole blood from a healthy donor of the Naka-negative phenotype, whose platelets constitutively lack CD36, over collagen-coated coverslips. In this case, percent surface coverage was 55% of normal controls at 2 minutes, 76% of controls at 5 minutes, and 72% of controls at 10 minutes. In both preparations, platelets lacking functional CD36 had a statistically significant decrease (P < .005) in adhesion after 2 minutes and 10 minutes perfusion but not at 5 minutes. These results show that functional CD36 facilitates the rapid adhesion of platelets to collagen and that this effect is seen at the earliest time points of their interaction.

Antibodies↗
PubMed1993

Platelet adhesivity to subendothelium is influenced by polymorphonuclear leukocytes: studies with aspirin and salicylate.

Interactions between blood platelets and polymorphonuclear leukocytes (PMN) influence cell reactivity. We have examined the effects of inhibiting platelet and PMN cyclooxygenase and lipoxygenase pathways, by treatment with aspirin (ASA) and salicylate (SAL) on platelet-vessel wall interaction studied under flow conditions by means of an annular chamber perfusion system. We have also measured the levels of cyclooxygenase-derived metabolites during perfusion. Perfusates were prepared with untreated and ASA- or SAL-treated PMN or platelets. Our results demonstrated that blockage of the lipoxygenase pathway in PMN significantly increased platelet thrombus formation and favored the production of thromboxane B2 (TxB2) during perfusion, whereas inhibition of cyclooxygenase pathway in PMN had no effect either on platelet deposition or on TxB2 levels. In contrast, blockage of platelet cyclooxygenase, which caused almost total inhibition of TxB2, enhanced platelet adhesion and did not modify platelet thrombus formation. These results suggest that under dynamic conditions cooperative metabolic mechanisms between platelets and PMN directly influence platelet interaction with vascular subendothelium.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Prothrombin fragment 1 + 2 and thrombin-antithrombin complex measurements indicate continuous and progressive intraoperative thrombin generation in liver transplantation.

Prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complex (TAT) have been measured in the different surgical phases in 40 patients undergoing 43 orthotopic liver transplantations (OLT), in order to study thrombin generation throughout the surgical procedure. F1 + 2 and TAT progressively rose from preoperative values (1.47 +/- 0.92 nmol/l and 22.41 +/- 19.15 ng/ml, respectively) to the end of anhepatic phase (5.97 +/- 2.20 nmol/l, 64.24 +/- 11.30 ng/ml), whereas changes in circulating antithrombin III (ATIII) were negligible in this period. Thrombin generation continued to slightly but significantly increase immediately after liver graft reperfusion (F1 + 2 6.87 +/- 1.65 nmol/l, TAT 89.32 +/- 7.54 ng/ml), and ATIII levels decreased from 70.61 +/- 12.28 to 57.16 +/- 9.57%. Higher preoperative values of F1 + 2 were associated with larger requirements of both packed red blood cells and fresh frozen plasma (FFP) in the host liver explantation phase, whereas the lowest basal levels of ATIII were related to a higher plasma expense in the whole OLT procedure. The activation of circulating prothrombin begins early in OLT, and adequate FFP infusion is capable of maintaining appropriate circulating thrombin-inhibitory activity.

Adolescent↗