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.

Estratificación del riesgo de enfermedad tromboembólica venosa y tromboprofilaxis con heparina de bajo peso molecular en pacientes sometidos a cirugía mayor ambulatoria. Estudio prospectivo observacional / Venous thromboembolism risk stratification and thromboprophylaxis with low molecular weight heparin in patients undergoing major ambulatory surgery: an observational prospective study

Introducción: el riesgo de enfermedad tromboembólica venosa (ETV) después de cirugía mayor ambulatoria (CMA), aunque supuestamente es bajo, continua siendo desconocido. Esta cirugía, que cada vez es más frecuente y extensiva a pacientes de mayor edad y comorbilidad, nos obliga a buscar pacientes de riesgo. El objetivo es validar de forma prospectiva una estratificación del riesgo de ETV, en pacientes de CMA, lo que determina el tipo de tromboprofilaxis a realizar. Pacientes y métodos: estudio prospectivo en 402 pacientes consecutivos (45,1 ± 16,0 años) sometidos a diversos procedimientos de CMA, fundamentalmente de pared abdominal (82%) y bajo anestesia regional (60,5%). Los pacientes son estratificados según un consenso español en: a) sin riesgo ETV (n = 141 pacientes); b) con riesgo moderado (n = 228), o c) alto (n = 33). Los grupos de riesgo moderado y alto recibieron heparina de bajo peso molecular (bemiparina 2500 o 3500 UI), comenzando 6 horas después de la operación durante siete días. Al décimo día del postoperatorio se realizo eco-doppler color (de forma ciega), el cual se repitió a la semana en caso necesario; a los 10 y 30 días se midieron diversos parámetros de eficacia y seguridad. Se realizo un estudio trombofílico preoperatoriamente a un tercio de la muestra con la intención de conocer cómo modificaría a posteriori la estratificación realizada. Resultados: completaron el estudio 357 pacientes (88,8%). No se observó ningún evento sintomático; en el grupo de riesgo moderado se detectó una (..) (AU)

Although supposedly low, the risk of venous thromboembolism (VTE) after major ambulatory surgery (MAS) remains to be established. We have carried out a prospective validation of the risk stratification of VTE in MAS patients. Methods: 402 consecutive patients were stratified according to a Spanish consensus as: a) no risk of VTE (n = 141), b) moderate risk (n = 228), and c) high risk (n = 33). The moderate and high risk groups received thromboprophylaxis with low molecular weight heparin. On post-operative day 10, a colour Echo-Doppler was obtained; on days 10 and 30 different parameters of efficacy and safety were measured. Results: 357 patients completed the study. No symptomatic events were observed; one case of asymptomatic deep vein thrombosis was observed. Overall, in 39 patients (three from the low risk group and 36 in the moderate and high risk groups; p<0.001) a decrease to 15 cm/s was observed in interior femoral blood flow. Haemorrhagic complications, all of them minor, in the surgical wound accounted for 2%. The study of thrombophilia revealed a high number of patients with hidden thrombophilia (28.1%). Conclusion: MAS patients are not free of VTE events and require risk stratification. Thromboprophylaxis with LMWH in moderate and high risk of VTE is safe and effective (..)(AU)

Influencia de la mutación C677T del gen de la metilentetrahidrofolato reductasa en la enfermedad tromboembólica venosa / Influence of the C677T mutation in methylenetetrahydrofolate reductase gene in venous thromboembolic disease

La enfermedad tromboembólica venosa (ETV) es considerada como una enfermedad multifactorial. Es necesaria la presencia de factores genéticos, que predisponen al individuo a la trombosis, y factores ambientales, que desencadenan la trombosis (interacción gen-ambiente). En los últimos años se han descrito numerosos polimorfismos asociados con un mayor o menor riesgo a padecer una enfermedad trombótica en sus distintas variantes. Una de estas mutaciones de interés es la C677T del gen metilentetrahidrofolato reductasa (MTHFR), que consiste en la sustitución de una citosina por una timina en el nucleótido 677. Este cambio de aminoácido genera una variante de MTHFR termolábil con capacidad reducida para metabolizar la homocisteína, pudiendo aparecer una hiperhomocisteinemia leve-moderada, factor de riesgo conocido en la ETV. Por tanto, C677T MTHFR podría predisponer a la aparición y recurrencia de la ETV. Este artículo pretende analizar el papel concreto desempeñado por este polimorfismo en la ETV, así como su aplicabilidad clínica(AU)

Venous thromboembolism (VTE) is a multifactorial disease in which both environmental and genetic factors are involved. The presence of mutations in genes coding for haemostatic, fibrinolytic and, also, inflammatory proteins is associated with an increased risk of first episode and recurrence of venous thrombosis. So, in the last years, several polymorphisms associated with thrombosis have been reported. Recently, the 677C > T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene (a C > T substitution at base pair 677 leading to the exchange of alanine to valine) has been proposed by some studies to be a thrombophilic risk factor. This mutation causes moderate hyper-Hcy, and Hyper-Hcy is well known to cause VTE. We analysed the role of C677T MTHFR in VTE, as well as its clinical applicability(AU)

Pharmacogenetics of acenocoumarol in patients with extreme dose requirements.

SUMMARY BACKGROUND: There is currently intense debate as to whether pharmacogenetic algorithms for estimating the initial dose of coumarins provide a more accurate dose than the fixed-dose approach. Recently, it has been suggested that the greatest benefit of pharmacogenetic algorithms is observed in patients with extreme dose requirements. OBJECTIVES: To identify clinical and genetic factors that better characterize patients who need extreme acenocoumarol doses for steady anticoagulation state. PATIENTS/METHODS: We reviewed 9538 patients with a steady acenocoumarol dose from three Spanish hospitals, selecting 83 who took or= 30.00 mg week(-1) (p95). We also selected patients matched by gender and age taking 13.50-14.00 mg week(-1) (p50). We genotyped VKORC1 (rs9923231), CALU (rs1043550), GGCX (rs699664), CYP2C9 (rs1799853; rs1057910), CYP4F2 (rs2108622) and F7 (rs5742910) single-nucleotide polymorphisms (SNPs). RESULTS: Comparison between p5 and p95 revealed five parameters with significant differences: body surface area (BSA) (P = 0.006), age, VKORC1, CYP2C9 and CYP4F2 genotypes (all P < 0.001). First VKORC1, and second, CYP2C9 SNPs played a strong effect by determining extreme doses, particularly in p95. Only one out of 203 p95 had the VKORC1 A-1639A genotype, but this subject was CYP2C9*1/*1. In contrast, nine out of 83 p5 carried the VKORC1 G-1639G genotype, although six of them were CYP2C9*3 homozygotes and another two were heterozygotes. Surprisingly, CYP4F2 V433M SNP displayed prevalences that suggest that its influence might only be evident when patients are treated with high doses. CONCLUSION: Two clinical data, age and BSA, and three SNPs in the VKORC1, CYP2C9 and CYP4F2 genes strongly predict outlier patients treated with acenocoumarol.

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.

Hyperhomocysteinemia is a risk factor of recurrent coronary event in young patients irrespective to the MTHFR C677T polymorphism.

Despite the well-known pro-coagulant effect of hyperhomocysteinemia, data is limited regarding the result on recurrent coronary event (RCE) in young people. One hundred and forty patients <55 years old with a first acute coronary syndrome (ACS) were prospectively followed for a mean (+/-S.D.) follow-up of 49+/-14 months in order to investigate the relationship between homocysteine levels (tHcy) at admission and the incidence of RCE. The tHcy values were divided into quartiles to examine their relationship with end points. Furthermore, we determined the effect of C677T methylene tetrahydrofolate reductase (MTHFR) polymorphism, as well as other risk factors for developing a RCE. The median plasma homocysteine concentration was 9.6 mumol/L (interquartile range, 3.7). In the screening of MTHFR C677T polymorphism in patients with ACS, the T allele frequency was 0.4 and the genotype frequency distributions were in Hardy-Weinberg equilibrium. At time of final evaluation, 49 (35%) of the 140 valuable patients had developed a RCE. Increasing numbers of RCE were observed for increasing quartiles of tHcy according to Kaplan-Meier survival (Log-rank test=0.0092). The MTHFR C677T polymorphism was not associated with an increased incidence of RCE. In multivariate analysis, the variables independently associated with a higher risk of RCE were age older than 45 years [HR=2.7; (95% CI, 1.3-6.1); p=0.030], body mass index more than 25 [HR=2.6; (95% CI, 1.1-5.9); p=0.034] and tHcy levels into quartile 4 (tHcy>12.37 mumol/L) [HR=2.5; (95% CI, 1.1-4.7); p=0.04]. Elevated plasma homocysteine level at admission is an independent risk factor for RCE after the first episode of ACS in young patients irrespective of the status of MTHFR C677T.

Partial androgen deficiency in aging type 2 diabetic men and its relationship to glycemic control.

Aging in the male is associated with both a higher incidence of type 2 diabetes and hypogonadism. However, little information is available about the complex of symptoms and hormonal changes related to partial androgen deficiency in aging (called andropause) in type 2 diabetic men. Here, for the first time, we used a combination of clinical and hormonal criteria to define andropause and to analyze the relationships between the androgen environment and glucose metabolism in 55 type 2 diabetic men (63.6 +/- 7.9 years, mean +/- SD). Low plasma levels of total testosterone (< or =3.4 ng/mL) and free testosterone (< or =11 pg/mL) were found in 20% and 54.5%, respectively, of the diabetic men. The fraction of diabetic men with subnormal levels of total testosterone increased with aging: 14.2% (50 to 59 years), 17.4% (60 to 69 years) and 36% (> 70 years). The corresponding figures for subnormal values of free testosterone were 38%, 69.6%, and 54.5%, respectively. In the whole group of type 2 diabetic men, no significant linear correlations between total or free testosterone with fasting plasma glucose, insulin, C-peptide, or fructosamine values could be established. Total testosterone was positively correlated with glycosylated haemoglobin (HbA(1c)) levels (r =.322, P =.01). Although fasting plasma glucose was marginally higher in aging type 2 diabetic patients with andropause than in those without andropause (162 +/- 6.9 v 139 +/- 8.9, mean +/- SEM, P =.05), there were no differences between both subgroups for plasma fasting insulin, C-peptide, fructosamine, or HbA(1c) levels. Replacement therapy (150 mg intramuscular [IM] of enanthate of testosterone every 14 days for 6 months) was applied in 10 type 2 diabetic men with clinical features of andropause associated with subnormal concentrations of serum testosterone. The treatment induced significant increases in total plasma testosterone (baseline: 3.9 +/- 0.3; at 6 months: 7.1 +/- 0.9 ng/mL, mean +/- SEM, P =.003) and free testosterone (baseline: 9.3 +/- 0.6; at 6 months 17.6 +/- 2.4 pg/mL, P =.003), but had a neutral effect on overall glycemic control. These data show a high prevalence of andropause in aging type 2 diabetic men and suggest that the endogenous androgen environment, as well as correction of the partial androgen deficiency, do not have a meaningful effect on glycemic control.

Antiphosphatidylserine antibodies in patients with autoimmune diseases and HIV-infected patients: effects of Tween 20 and relationship with antibodies to beta2-glycoprotein I.

Antiphospholipid antibodies (aPL) react with negatively charged phospholipids, which may often be complexed with a protein cofactor such as beta2 glycoprotein (beta2GPI) and prothrombin. Cofactor requirements may be assessed by measuring antibodies to beta2GPI or by adding Tween 20 to some reagents in the assays for aPL (anticardiolipin and antiphosphatidyIserine). We have measured anticardiolipin antibodies (aCL), antiphosphatidylserine antibodies (aPS), and anti beta2 glycoprotein antibodies (abeta2GPI) in the serum of 10 normal subjects, 20 patients with systemic autoimmune diseases (SAD) diagnosed as having systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS), and 12 patients with HIV infection. Adding Tween 20 to aPS, the assay couldn't differentiate protein cofactor dependent from independent antibodies, but this can be done by measuring abeta2GPI (P= 0.0008). There was a significant correlation between aCL and a(beta)2GPI in the control group and in the patients with SAD, but not in the HIV-positive (HIV+) patients. After excluding the HIV+ patients, the best Spearman correlation was obtained between a(beta)2GPI and aCL (0.64, P< 0.0005). In 3 out of 7 patients with positive a(beta)2GPI and in 5 out of 6 patients with moderate or high positive aCL of the group of SAD, there was a history of venous thrombosis. The presence of moderate or high values of aCL either alone or together with a(beta)2GPI was significantly associated with a history of venous thrombosis (P < 0.05). Moderate or high aCL concentrations and their association with a(beta)2GPI seems to be useful for the assessment of the risk of venous thrombosis in unselected patients with SLE or APS.

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.

Natural anticoagulant proteins and antiphospholipid antibodies in systemic lupus erythematosus.

OBJECTIVE: Thrombosis is a relatively common complication in patients with systemic lupus erythematosus (SLE) and is strongly associated with the presence of antiphospholipid antibodies (aPL). The mechanism involved in the pathogenesis of this prothrombotic state remains obscure. We studied 4 natural anticoagulant proteins: protein C, protein S, antithrombin III, and plasminogen in 50 patients diagnosed with SLE. METHODS: Protein C, antithrombin III, and plasminogen were measured by chromogenic substrates and total and free protein S by electrophoresis. We also determined the prevalence of different aPL (lupus anticoagulant and antibodies against cardiolipin, phosphatidylserine, and phosphatidylinositol). RESULTS: Ten patients (20%) had a history of thrombosis. Some type of aPL was present in 26 patients (52%). Nine of the 10 patients with history of thrombosis had aPL (p = 0.007). Functional assays for protein C, antithrombin III, and plasminogen were in the normal range in all patients. Low free protein S levels were documented in 19 patients and were associated with the presence of aPL (13/19 were aPL positive) (p < 0.05). Only 4 patients with acquired free protein S deficiency had a history of thrombosis. CONCLUSION: This study shows an association between aPL and reduced free protein S levels in patients with SLE. Further studies are needed to determine the mechanism and role of this acquired deficiency in the pathogenesis of thrombotic episodes in patients with SLE.

[Control of oral anticoagulant treatment using an automated method]. / Control del tratamiento con anticoagulantes orales mediante un método automatizado.

PURPOSES: To evaluate the reproducibility of an automated method (IL test Pro-IL-Complex) in the control of oral anticoagulant therapy. PATIENTS AND METHODS: Samples from patients subjected to oral anticoagulants were analysed with two different methods in order to compare the International Normalized Ratio (INR). The results were studied with the regression analysis and the statistical SPSS programme. RESULTS: Two INR values were attained in 422 samples studied with Thrombotest and Pro-IL Complex. The correlation coefficient (r) between both values was 0.94. When establishing anticoagulation limits of 2.0 and 4.8 for Thrombotest and 1.66 and 4.2 for Pro-IL Complex, the percentage of coincidence between the two methods was above 90%. These findings were more evident when analysing separately those patients with coronary or vascular disease subjected to chronic anticoagulant treatment. CONCLUSIONS: These findings show that Pro-IL Complex test renders results similar to those attained with Thrombotest. Since the former is an automated method available for most of the coagulometers used in clinical laboratories, its easy management, rapidity and possibility for using computerized data are most valuable.

[Primary antiphospholipid syndrome in juvenile ischemic stroke]. / Síndrome antifosfolipídico primario en el ictus isquémico juvenil.

Results obtained in three patients with juvenile ischemic stroke and criteria of primary antiphospholipid syndrome is reported. These patients are selected out from a series of 12 patients with 18-mounts follow-up. Lupic anticoagulant and anticardiolipin antibodies were found in two of three patients and one patient show anticardiolipin antibodies with negative lupic anticoagulant. All others coagulation proteins examined (antithrombin III, plasminogen, protein C and protein S) were normal. We conclude that antiphospholipid antibodies are associated with increase risk of thrombosis. Therefore should be systematically investigated in juvenile ischemic stroke of unknown aetiology.

Incidence and clinical characteristics of hereditary disorders associated with venous thrombosis.

At present, different congenital defects in several proteins--antithrombin III (AT III), protein C (PC), protein S (PS), and plasminogen (PLG)--are known to be causes of hereditary predisposition to thrombosis (thrombophilia). The incidence of these hereditary disorders in our 204 patients (106 males and 98 females) with venous thromboembolism were 4% (three cases deficient in PC, three in PS, two in PLG, and one patient in AT III). Their families were studied. In all cases the disorders were inherited as an autosomal dominant trait. The first thrombotic episodes occurred at a age of below 40 years. There was no relationship between protein levels and the occurrence of thrombosis, although a significant relationship was observed between a positive history of thromboembolic disease and a diagnosis of protein deficiencies. We evaluated the differences between primary thrombosis and secondary thrombosis. The most common thrombotic sites were the deep veins. There were no differences between males and females. Evaluation of PC, PS, AT III, and PLG in patients with thromboembolic disease should be considered.

[Antibodies against hepatitis C virus in hemophiliacs: correlation with peripheral blood lymphocyte populations]. / Anticuerpos frente al virus de la hepatitis C en hemofílicos: correlación con las poblaciones linfocitarias de sangre periférica.

The presence of antibodies (Abs) against hepatitis C virus (HCV) was analyzed in 26 haemophiliac patients; a prevalence of 38% was found in the total series and 56% in the treated patients. There were no cases with a positive serology among the three patients who had only received pasteurized factor. The frequency of detection of anti-HCV was higher in the patients who had a positive serology for HIV (67%) and hepatitis B virus (56%) than in the seronegative patients (24 and 29%, respectively). The patients with HCV Abs showed a decrease in the helper (CD4+) lymphocytic population, mainly due to the decrease in the helper inducer (CD4+/Leu8-) cells, such alterations being more evident in the patients who also were HIV+ who showed as well an increase in the T-cell activated lymphocytes (CD3+/la+) and a decrease in CD16+ natural killer cells. These results suggest that the lymphocytic alterations found in the patients with anti-HCV Abs are not specific and would rather be related to the presence or not of HIV infection.

Subcutaneous desmopressin (DDAVP) shortens the prolonged bleeding time in patients with liver cirrhosis.

The intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) shortens the prolonged bleeding time in patients with congenital or acquired bleeding disorders, including patients with uremia or liver cirrhosis. We carried out a double-blind, placebo-controlled crossover study in ten patients with liver cirrhosis to evaluate whether or not their prolonged bleeding times could be shortened by subcutaneous injections of DDAVP (0.3 microgram/kg), a more practical route of administration than intravenous infusions. One hour after DDAVP injection the bleeding time was significantly shortened (p less than 0.05). After 4 h, however, the bleeding time shortening was no longer statistically significant. There was no bleeding time change after placebo. Plasma levels of von Willebrand factor antigen (vWF:Ag) did not significantly increase after DDAVP or placebo. The study shows that subcutaneous DDAVP is an alternative method for short-term shortening of the bleeding time in liver cirrhosis.