Blood rheology and renal transplantation: an intriguing relationship for assessing cardiovascular risk.

Renal transplant recipients (RTRs) are at increased risk of cardiovascular complications. An altered hemorheological profile may determine both cardiovascular complications and progression of renal failure in RTRs. We performed this study to evaluate the rheologic status in 239 RTRs at least 12 months after transplantation with stable and normal renal function compared with 90 control subjects. In RTRs, a significantly higher hematocrit-adjusted, but not native, whole blood viscosity was found (P < .0001). Moreover, plasma viscosity and red blood cell deformability were significantly higher in patients than in control subjects (P < .0001), whereas no difference in erythrocyte aggregation between patients and control subjects was observed (P = .5). Fibrinogen, but not hematocrit, significantly increased in RTRs (P = .001). This preliminary study provides evidence of an altered hemorheologic profile in RTRs.

Lipoprotein (a) and anticardiolipin antibodies are risk factors for clinically relevant restenosis after elective balloon percutaneous transluminal coronary angioplasty.

Recent reports have shown the importance of new risk factors for cardiovascular disease. We investigated the relationship between Lp(a), fibrinolytic parameters and anticardiolipin antibodies (aCL) and the occurrence of clinical recurrence owing to restenosis after elective balloon percutaneous transluminal coronary angioplasty (PTCA) without stenting. In 167 patients, undergoing PTCA, Lp(a) plasma levels, aCL, euglobulin lysis time (ELT), plasminogen activator inhibitor-1 (PAI-1) activity and tissue-type plasminogen activator (t-PA) plasma levels were evaluated before the procedure. During follow-up 29 patients underwent clinical recurrence due to restenosis. Lp(a) levels were significantly higher in patients with restenosis in comparison to those without (P<0.05); an earlier restenosis was observed in patients with Lp(a) values >450 mg/L. Kaplan-Meier survival estimate showed an earlier occurrence of restenosis in patients with base-line Lp(a)>300 mg/l associated with aCL positivity. High Lp(a) plasma levels play a role in the occurrence of clinical recurrence due to restenosis after elective balloon PTCA without stenting; the association with aCL accelerates the development of restenosis.

Activated protein C resistance is a risk factor for central retinal vein occlusion.

Central retinal vein occlusion is one of the most common retinal vascular disorders. Few and contrasting data are available on the prevalence of hemostatic risk factors in patients with central retinal vein occlusion. The aim of this study was to investigate the most common hemostasis-related inherited risk factors for venous thrombosis in a group of 53 central retinal vein occlusion patients (median age 59 years, range 18-77 years) and in 53 comparable control subjects (median age 57 years, range 22-84 years). No difference was found in antithrombin III, protein C and protein S plasma levels between patients and controls. At univariate analysis, activated protein C resistance (odds ratio 5.8) and factor V Leiden (odds ratio 4.4) were significantly associated with central retinal vein occlusion whereas G20210A polymorphism of the prothrombin gene was not. After adjustment for sex, age, and the other classic vascular risk factors (hypertension, diabetes, hypercholesterolemia, smoking) activated protein C resistance remained the only independent risk factor for central retinal vein occlusion (odds ratio 11.5). These data indicate that activated protein C resistance may play a role in the pathophysiology of central retinal vein occlusion.

Evaluation of clotting and fibrinolytic activation after protracted physical exercise.

The behavior of hemostatic system activation during protracted physical exercise is well known, but the duration of its modification is not yet defined. In order to evaluate the time of hemostatic system activation after prolonged strenuous endurance physical exercise (typical marathon race: 42.195 km, v=15.35 km/h; mean length of time run 2.45+/-0.15 hours) 12 well-trained long-distance male runners (mean age: 35+/-7, range 25-47 years) were investigated. Blood samples were drawn in the morning on the day before the performance, immediately after the race, and 24 hours and 48 hours after the end of run. With respect of baseline, immediately after the race, a significant decrease of fibrinogen (-25%) and significant increases of prothrombin fragment 1+2 (+633%) and thrombin-antithrombin complex (+848%) were observed. A significant acceleration of euglobulin lysis time (-41%), and rises of plasma levels of tissue plasminogen activator antigen (+361%), plasminogen activator inhibitor type 1 antigen (+235%), d-dimer (+215%), and plasma fibrinogen degradation products (+1200%) were also found. Only a slight, yet not significant, decrease in plasminogen activator inhibitor type 1 activity was observed. One day after the end of marathon different parameters were still unchanged. Forty-eight hours after the competition all parameters investigated returned to baseline values. These results indicate a persistence of clotting as well as fibrinolysis activation up to 24 hours after the end of the race.

Persistence of hemostatic alterations in patients affected by Crohn's disease after bowel surgery.

In Crohn's disease (CD) a condition of hypercoagulability with increased risk for thrombotic events has been reported. In this study we have investigated hemostatic parameters in thirty-one patients affected by CD before, 3 and 12 months after bowel operation, and in thirty healthy controls. Before surgery platelet number (PLT), fibrinogen (Fbg), prothrombin fragment F1 + 2 (F1 + 2), PAI and whole blood-spontaneous platelet aggregation (WB-SPA) were significantly higher (p at least < 0.0005) in patients than in controls, while factor XIII (F XIII) was significantly lower (p at least < 0.005). Three and twelve months after surgery PLT, FBG and WB-SPA significantly decreased in comparison to pre-surgery values (respectively p at least < 0.05 and p < 0.01), but PLT and Fbg were still significantly higher than in controls at 3 and 12 months (p < 0.01). At three and 12 months after operation F XIII was significantly higher in comparison with pre-surgery values (p at least < 0.05). The presence of antiphospholipid antibodies (aPL) was not different between CD patients and controls before surgery, whereas it significantly increased 12 months after surgery (p < 0.05). Our results suggest that in CD hemostatic changes are only in part influenced by local flogistic processes and that an inflammatory systemic condition may provoke both the bowel and extraintestinal manifestations of CD.

Blood clotting activation during normal pregnancy.

Pregnancy is considered as a hypercoagulable state and an increased incidence of thromboembolic phenomena has been reported in pregnant women. Relevant changes in the hemostatic mechanism have been reported during physiological pregnancy: briefly, increased levels of coagulation factors, enhanced thrombin generation and suppression of fibrinolysis are commonly found in women with uncomplicated pregnancy. We recently described progressive increases in fibrinogen and D-dimer plasma levels during normal pregnancy. The increase in D-dimer levels makes difficult their interpretation for the exclusion of thromboembolic phenomena in pregnancy. The behavior of prothrombin fragment 1+2 (F1+2) levels during physiological pregnancy is scarcely known. The aim of this preliminary study was to establish range values of F1+2 plasma levels for different periods of normal pregnancy.

Antiphospholipid antibodies and pregnancy disorders in women with insulin dependent diabetes.

Insulin dependent diabetes (IDD) is considered to be an immune endocrinopathy as in such patients a disorder of the immune system is involved; however, up to now no data are available on the occurrence of antiphospholipid antibodies (aPL) in IDD pregnant women and on possible correlation between the presence of aPL and the high fetomaternal morbidity reported in these patients. The presence of lupus anticoagulant (LA) and of anticardiolipin antibodies (ACA) was monthly evaluated. In 35 IDD pregnant women referring within the 7 degrees week of pregnancy to the High Risk Pregnancy Medical Unit. Levels of D-dimer, fibrin degradation product, were also assayed. Twelve IDD pregnant women resulted to be aPL positive with a markedly high prevalence of positivity (34%). aPL positive did not significantly differ from aPL negative women in age, duration and severity of diabetes and in metabolic control throughout pregnancy. Pregnancy induced hypertension (PIH) and intrauterin growth retard (IUGR) were observed in 6/12 aPL positive and in only 2/23 aPL negative patients (p < 0.02). A pathological increase in D-dimer levels occurred in 6/12 aPL positive patients and in none aPL negative (p < 0.03). The high frequency of aPL positivity and its strict relation to pregnancy complications strongly support a major role for an autoimmune pathogenetic mechanism in the occurrence of feto-maternal morbidity in IDD pregnant women. The identification of this subgroup at risk for complications may be clinically relevant.

Hemostatic abnormalities in inflammatory bowel disease.

Patients affected by inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. Aims of this study were to investigate hemostatic system and the presence of antiphospholipid antibodies (aPL) in IBD patients. Forty-one patients affected by Crohn's disease (CD) and 19 by ulcerative colitis (UC) were studied, compared to 40 healthy control subjects. Platelet count (PLT), PT, aPTT, fibrinogen (Fib), prothrombin fragment F1+2, antithrombin (AT), protein C (PC), protein S (PS), factor XIII (FXIII), plasminogen (PLG), plasminogen activator inhibitor (PA1), spontaneous platelet aggregation in platelet-rich plasma (PRP-SPA) and in whole blood (WB-SPA), and antiphospholipid antibodies (aPL) were evaluated. PLT, Fib, F1+2 and WB-SPA were significantly increased in IBD patients (p at least <0.05) both in active and inactive phases; aPL positivity was more frequent (p<0.05) and FXIII was significantly decreased (p<0.05) in comparison to control subjects. The thrombophilic state of IBD patients is not related to the degree of activity of the disease or to previous thrombotic events; aPL express the immunological alterations connected with IBD and are not the main cause of thrombotic events.

Clottable to immunological fibrinogen ratio in plasma from control subjects and hyperfibrinogenemic patients.

The measurement of fibrinogen (Fg) plasma levels is one of the more frequently performed tests in clinical practice, usually by clotting assay. However, for the diagnosis of dysfibrinogenemia the use of an immunological assay is necessary to compare total and clottable protein. Little information is available on the range of the ratio clottable (C) Fg/immunological (I) Fg levels in normal population. This study aimed at evaluating the CFg/IFg ratio in 70 control subjects (age range 17-74 years-group A), in 57 acute patients (age range 17-79 years-group B) and in 14 pregnant women (age range 27-41 years, pregnancy weeks 30-40-group C), as a physiologic model of hyperfibrinogenemia. CFg was assayed on citrated plasma by the Clauss clotting method and IFg was assayed by radial immunodiffusion technique. In the three groups, CFg/IFg ratios were not significantly different (respectively group A 0.98 +/- 0.17, group B 1.02 +/- 0.18 and group C 1.01 +/- 0.11), whereas both CFg (310 +/- 45 mg/dl) and IFg (326 +/- 70 mg/dl) levels were lower (p < 0.001) in control subjects than in patients (CFg 556 +/- 92 mg/dl; IFg 561 +/- 121 mg/dl) and in pregnant women (CFg 530 +/- 65 mg/dl; IFg 530 +/- 77 mg/dl). The analysis of the relationship between CFg and IFg in the three groups (group A: y = 11.53 + 1.01x, r = 0.64, p < 0.001; group B: y = 68.72 + 0.88x, r = 0.67, p < 0.0001; group C: y = 71.59 + 0.87x, r = 0.73, p < 0.01) indicates that a good correlation exists (p < 0.001) for values of fibrinogenemia ranging from 180 to over 700 mg/dl. A reference range of CFg/IFg (mean +/- 2 SD in group A) was 0.64-1.32. These data could be of practical importance for a rapid screening of dysfibrinogenemias.

D-Dimer in intra-uterine growth retardation and gestational hypertension.

Pregnancy is sometime related to thromboembolic complications (1) and alterations in different hemostatic parameters have been reported in pregnancy (2-4). In particular, a progressive increase in fibrinogen and D-dimer levels occurs during normal pregnancy (5-9). D-dimer levels may be predictive for some complications such as preeclampsia (10) and they have been also reported to be useful for diagnosis of abruptio placentae (6). However, it remains to be established if common ELISA for D-dimer are able to discriminate pathologic samples in conditions such as intrauterine growth retardation (IUGR) or gestational hypertension (GH). Aim of the present study has been to evaluate the behavior of D-dimer in pregnant women with IUGR and GH.

D-dimer concentrations during normal pregnancy, as measured by ELISA.

In pregnant women a number of changes in blood clotting and fibrinolysis proteins have been reported so indicating the existence of a state of hypercoagulability. In addition to fibrinogen and antithrombin III (AT), D-dimer is frequently checked during pregnancy, in particular during at risk pregnancy, but the exact pattern of D-dimer modifications during uncomplicated pregnancy is not definitively described. The aim of this study was to establish the range values in three different periods of uncomplicated pregnancy (A: 1-20 wks; B: 21-30 wks; C: 31-40 wks). We measured plasma levels of D-dimer, clottable fibrinogen and AT in 108 consecutive normal pregnant women aged 16 to 42 years. In period A, the range of D-dimer values was 43-211 ng/mL, not different from controls, while fibrinogen levels were significantly higher (p < 0.05) than in matched non pregnant women. Mean D-dimer levels were higher in periods B (p < 0.05) and C (p < 0.05) vs period A. Similarly, mean fibrinogen levels were found more elevated in periods B and C vs period A (p < 0.05). A significant correlation was found between fibrinogen and D-dimer levels (p < 0.001). No differences in AT levels were found among the three periods of pregnancy. The results of this study indicate that levels of D-dimer up to 685 micrograms/L may be reached at the end of physiological pregnancy. This fact should be taken into account in the evaluation of hemostatic studies performed in uncomplicated and complicated pregnant women.

Acute phase proteins in alcoholics with or without liver injury.

Acute phase proteins behaviour has been examined in chronic alcoholics to verify the hypothesis that chronic alcohol consumption stimulates the hepatic synthesis of acute phase proteins. Certain acute phase proteins were studied in two groups of alcoholics, one with and one without liver damage, and in a third group of healthy volunteers. The results show that the acute phase proteins were similar in the two groups of alcoholics, but differed when compared to the control group. The authors have concluded from these results, that chronic alcohol consumption causes a serum increase of: mucoproteins (p less than 0.001), alpha 1 acid glycoprotein (p less than 0.05), haptoglobin (p less than 0.05) and fibrinogen (p less than 0.02). Such increases are independent from the existence of liver damage.