Slow femoral venous flow and venous thromboembolism following inguinal hernioplasty in patients without or with low molecular weight heparin prophylaxis.

BACKGROUND: Prosthetic material (mesh) is commonly used to repair inguinal hernias. Its implantation close to the common femoral vein (CFV) can induce slow flow and favor the appearance of venous thromboembolism (VTE) events. AIM: To investigate the speed of flow, diameter and area of the CFV after inguinal hernioplasty. METHODS: Two hundred and fifty patients receiving open hernioplasty with a non-resorbable mesh for the repair of a unilateral, primary, simple inguinal hernia were prospectively investigated. Patients were stratified, by consensus, into a low or a moderate risk of VTE group. The moderate-risk group (n = 163) received low molecular weight heparin. On day 10 post-operation a blinded Echo-Doppler was carried out, and repeated 7 days later in patients with a venous flow of <15 cm/s. The speed of flow (cm/s), diameter (cm), and area (cm(2)) of the ipsilateral and contralateral CFV of the groin operated upon were measured. RESULTS: No event symptomatic of VTE was documented. One case of asymptomatic deep vein thrombosis (1/163, 0.6%) was found in the moderate-risk group. In 29 patients (2 and 27 in the low- and moderate-risk groups, respectively; p < 0.001) a maximum blood flow velocity of <15 cm/s was found in the ipsilateral CFV; these flows were close to normal in the second measurement. Taking the entire sample into account, the maximum venous blood flow found in the ipsilateral CFV of the operated groin was less than that measured in the contralateral CFV (20.88 vs. 24.01 cm/s; p < 0.001); this difference was significant in both VTE risk groups. The diameter and area of the CFV were both greater in the ipsilateral than the contralateral CFV (p < 0.01); this finding proved to be significant only in hernias of the left groin (p < 0.001). CONCLUSIONS: In the immediate postoperative period, inguinal hernioplasty with mesh induces a temporarily slow venous flow in the ipsilateral CFV. However, this does not lead to an increase in the incidence of VTE.

Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a feared complication of allogeneic hematopoietic SCT (HSCT) owing to its high mortality rate. The use of calcineurin inhibitors or sirolimus (SIR) for GVHD prophylaxis has been suggested as a potential risk factor. However, the impact of tacrolimus (TAC) and SIR combinations on the increased risk of TA-TMA is currently not well defined. We retrospectively analyzed the incidence of TA-TMA in 102 allogeneic HSCT recipients who consecutively received TAC plus SIR (TAC/SIR) (n=68) or plus MTX (TAC/MTX)±ATG (n=34) for GVHD prophylaxis. No significant differences were observed in the incidence of TA-TMA between patients receiving TAC/SIR vs TAC/MTX±ATG (7.4% vs 8.8%, P=0.8). Only grade III-IV acute GVHD, previous HSCT and serum levels of TAC >25 ng/mL were associated with a greater risk of TA-TMA. Patients developing TA-TMA have significantly poorer survival (P<0.001); however, TA-TMA ceased to be an independent prognostic factor when it was included in a multivariate model. In conclusion, the combination of TAC/SIR does not appear to pose a higher risk of TA-TMA. By contrast, we identified three different risk groups for developing TA-TMA.

Clinical efficacy and safety of Flebogammadif, a new high-purity human intravenous immunoglobulin, in adult patients with chronic idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by a low platelet count and bleeding, whose incidence is approximately 6.2 for each 100,000 adults per year. Intravenous immunoglobulins (IVIG) can be useful in patients with ITP to prevent bleeding or prior to surgery. In this study, the efficacy and safety of Flebogammadif, a new high-purity IVIG, were assessed by an open, multicentre, non-controlled, prospective study in adult patients with chronic ITP. A total of 20 patients (enrolled if experiencing chronic ITP since at least 6 months before recruitment and if platelet count <20 x 10(9)L(-1) before treatment) received 0.4 g kg(-1)-bw of Flebogammadif for 5 consecutive days and were followed-up for 3 months. Efficacy endpoints were three: proportion of patients who reached a platelet count > or = 50 x 10(9)L(-1), time for the platelet count to reach that level and duration of response. Safety parameters [adverse events (AE), laboratory determinations and vital signs] and viral markers were regularly monitored. A total of 14 patients achieved a platelet count of > or = 50 x 10(9)L(-1). The median time to platelet response was or = 50 x 10(9)L(-1) was > or = 7 days. A regression of haemorrhages was reported for 17 patients on day 14. Eight patients presented 21 AEs (mostly mild) potentially related to the study drug. Neither abnormalities in laboratory values nor in viral markers were registered during the follow-up period. Flebogammadif was well tolerated and succeeded in providing a haemostatic platelet count in patients with ITP.

Changes in coagulation and fibrinolysis in the postoperative period immediately after kidney transplantation in patients receiving OKT3 or cyclosporine A as induction therapy.

Different immunosuppressive agents, in particular OKT3, have been implicated as causative factors in the risk for renal thrombosis in the period immediately after kidney transplantation. Also, in different types of vascular surgery, a state similar to hypercoagulation has been reported. To assess the extent to which OKT3, cyclosporine A (CsA), and surgery itself affect coagulation and fibrinolysis, a study was conducted of 20 patients divided into two groups: group A, 10 patients received OKT3 (first dose during the induction of anesthesia); and group B, 10 patients received CsA (first dose at least 2 hours before transplantation). Basal determinations and determinations at 2, 4, and 24 hours after the induction of anesthesia were made. No differences were found between the groups with respect to the clinical and usual coagulation parameters. The following were studied in both groups: (1) markers of coagulation activity (prekallikrein [PKK] levels and formation of thrombin-antithrombin complexes [TATc]), (2) inhibitors and suppressors of hemostasis (antithrombin III [AT-III] and protein C [PC] activity), (3) markers of fibrinolysis activation (levels of plasminogen [PLG] and of alpha2-antiplasmin [alpha2-APL]), and (4) markers of endothelial damage (tissue plasminogen activator [TPA] and thrombomodulin [TMD]). In both groups, an important formation of TATc was observed early, together with a decrease in PKK levels and consumption of both AT-III and PC, which reached their lowest levels at 24 hours. This points to an activation of coagulation through the intrinsic route and a secondary consumption of hemostasis inhibitors, both possibly caused by surgery. A consumption of PLG and alpha2-APL was also observed, reflecting stimulation of the fibrinolytic system and a physiological response to the activation of coagulation. A greater release of endothelial TPA was only observed in the patients receiving OKT3 (P < 0.0001), possibly signaling endothelial activation. It is concluded that surgical stress could be the major factor triggering the alterations seen in hemostasis and their possible consequences.

New congenital deficiency of high molecular weight kininogen and prekallikrein (Fitzgerald trait). Study of response to DDAVP and venous occlusion.

The prolonged partial thromboplastin time observed in the plasma of a 36 year old asymptomatic man was related to the reduced prekallikrein activities (coagulant; antigenic; and amidolytic) and the absence of coagulant and immunologic activities of high molecular weight kininogen (HMWKg). The patient's plasma also exhibited impaired surface-mediated fibrinolysis and impaired generation of kallikrein. The coagulation defect was identified as the "Fitzgerald trait". The levels of CH50, C2, C4 and C-1 inactivator were normal. Venous occlusion in the patient gave rise to a normal release of extrinsic plasminogen activator from the vascular endothelium. The administration of DDAVP led to a FVIII/VWF response which was similar to that obtained in healthy subjects. No alteration could be observed in the contact phase proteins after DDAVP administration.

Factor VIII-related antigen in cerebrospinal fluid.

A hundred and one samples of cerebrospinal fluid (CSF) were obtained from patients with bacterial meningitis (18), viral meningitis (9), lymphoproliferative disorders (33), 15 with meningeal infiltrations, multiple sclerosis (8), stroke (8) and 25 subjects with normal CSF. All samples were studied for VIIIR:Ag with specific and sensitive immunoradiometric assay (IRMA) and Laurell's technique. Prothrombin and factor IX antigenic activities were investigated by Laurell's technique. Simultaneously, plasma specimens from ten patients with bacterial meningitis were evaluated. Only a selective increase of VIIIR:Ag was demonstrated in CSF from bacterial meningitis whereas prothrombin and factor IX were not detected. VIIIR:Ag plasma and CSF levels were uncorrelated. Similarly, no relationship could be established between the degree of elevation of VIIR:Ag in the CSF and their protein concentration. These findings suggest that VIIIR:Ag elevation in CSF has diagnostic value for bacterial meningitis and that disruption of the blood-brain barrier is not responsible for their elevated levels. Accordingly, the presence of VIIIR:Ag in CSF may be an indication of endothelial damage in the choroid plexi.

Acute phase reactant proteins in differential diagnosis of monoclonal gammopathy.

The serum levels of five individual serum proteins, i.e. ceruloplasmin, alpha 1-antitrypsin, orosomucoid, haptoglobin and transferrin, were studied in 55 multiple myeloma (MM) patients, in 34 essential monoclonal gammopathy (EMG) patients, in 14 EMG patients excluded for active inflammatory process and in 14 healthy control subjects. Transferrin--negative acute phase reactant (APR)--was significantly decreased and the remaining proteins under study--positive APR--slightly increased in the EMG group compared with healthy controls. Transferrin and ceruloplasmin levels were significantly different when the MM was compared to the EMG group so that these parameters might be useful in differential diagnosis between both groups. In the MM clinical stage III, the differences are even more significant. In the IgG3 MM the APR levels seem to be more significantly changed than in the IgG1 and IgG2 MM. In EMG patients with active inflammatory process who were excluded ceruloplasmin, alpha 1-antitrypsin, orosomucoid and haptoglobin were significantly increased when compared with the EMG group.

[Renal disease in myeloma. Role of the tumor cell mass (author's transl)]. / Nefropatía del mieloma. Papel de la masa tumoral.

Out of a group of 57 patients with the diagnosis of multiple myeloma fourteen (25%) with different degrees of renal disease were selected. Bence-Jones (BJ) proteinuria, infections, and, above all, the tumoral cell mass were the three main factors implicated in the development of myeloma associated renal disease. Only 13% of IgG myelomas presented with renal failure as compared to 27% of IgA myelomas. The patients with BJ and IgD myeloma, classically those with a higher tendency to develop renal disease (in our series 37% of BJ myelomas and 50% of IgD myelomas had renal disease), had the biggest tumoral cell mass of all patients studied. The relationship between tumor cell mass and renal disease in myeloma is supported by the recovery of renal function in a patient with chronic renal failure after a treatment-induced reduction of the tumoral cell mass from 1.71 to 0.82 x 10(12) cells/m2 body surface.