Cirrhotic cardiomyopathy.

Decompensated liver cirrhosis is characterized by a peripheral vasodilation with a low-resistance hyperdynamic circulation. The sustained increase of cardiac work load associated with such a condition may result in an inconstant and often subclinical series of heart abnormalities, constituting a new clinical entity known as "cirrhotic cardiomyopathy". Cirrhotic cardiomyopathy is variably associated with baseline increase in cardiac output, defective myocardial contractility and lowered systo-diastolic response to inotropic and chronotropic stimuli, down-regulated beta-adrenergic function, slight histo-morphological changes, and impaired electric "recovery" ability of ventricular myocardium. Cirrhotic cardiomyopathy is usually clinically latent or mild, likely because the peripheral vasodilation significantly reduces the left ventricle after-load, thus actually "auto-treating" the patient and masking any severe manifestation of heart failure. In cirrhotic patients, the presence of cirrhotic cardiomyopathy may become unmasked and clinically evident by certain treatment interventions that increase the effective blood volume and cardiac pre-load, including surgical or transjugular intrahepatic porto-systemic shunts, peritoneo-venous shunts (LeVeen) and orthotopic liver transplantation. Under these circumstances, an often transient overt congestive heart failure may develop, with increased cardiac output as well as right atrial, pulmonary artery and capillary wedge pressures.

Rescue therapy by portal infusion of autologous stem cells in a case of drug-induced hepatitis.

Recent efforts have been directed toward new therapeutic options to approach drug-induced hepatitis. We report a case of acute liver failure associated with Nimesulide in a 67-year-old man, with a medical history of chronic alcohol abuse. The biopsy was compatible with chronic alcoholic liver disease and acute drug-induced injury. The patient was enrolled to receive G-CSF followed by apheresis and selection of peripheral-blood stem cells. After ultrasound-guided injection of CD34+cells in the portal vein, we observed a rapid improvement of synthetic liver function, with particular reference to coagulation parameters. Liver biopsy performed 20 days after, showed wide areas of regeneration. In the next 30 days the laboratory signs of acute decompensation progressively improved. Unfortunately he died of multiple-organ failure related to bacterial infection. Intrahepatic injection of peripheral-blood stem cells seemed safe and produced good periprocedural results with improvement of synthetic profile, suggesting a possible role of stem cells in the regeneration process.

Coagulation factor XIII Val34Leu gene polymorphism and Alzheimer's disease.

Blood coagulation factor XIII (FXIII) plays a role in inflammatory processes and a pathogenetic role of inflammation in neurodegenerative disorders has been proposed. FXIIIa subunit was immunohistochemically detected in a subpopulation of reactive microglia in Alzheimer's disease (AD). Aim of the present study is to evaluate whether a common polymorphism of the FXIII gene is associated with sporadic AD. We examined 90 patients affected by sporadic AD and 139 age- and sex-matched controls to assess the distribution of V/L alleles and genotypes of the FXIIIa-subunit gene. The LL genotype showed a significantly higher frequency in AD patients (p<0.05) with a significantly increased risk of AD in the presence of LL genotype at the logistic regression analysis [odds ratio: 3.6 (1.36-9.44), p<0.01]. This study shows for the first time an association between FXIII Val34Leu polymorphism and AD.

Growth hormone in inflammatory bowel disease.

Crohn's disease and ulcerative colitis are inflammatory diseases of the gastrointestinal tract characterized by chronic relapsing inflammation and catabolism. Growth hormone/insulin-like growth factor-I axis is important in inflammatory bowel disease, because of the effects on epithelial cell kinetics, collagen deposition and immunomodulation. The potential of growth hormone as a therapeutic option in inflammatory bowel disease has been proven in various clinical settings. Acquired growth hormone resistance in inflammatory bowel disease seems to be mediated by a combination of undernutrition and active inflammation. In particular, proinflammatory cytokines, such as TNF-a and interleukin-6, have been implicated as potential mediators of growth hormone resistance. The introduction of anti-TNF-alpha monoclonal antibodies has proven very efficacious in patients with inflammatory bowel disease. By reducing cytokines levels in inflammatory cells of intestinal mucosa, infliximab could interfere with cytokine-induced growth hormone resistance. Recent in vivo data have shown that acquired growth hormone resistance in patients with inflammatory bowel disease may be reversed after the administration of anti-TNF-alpha therapy.

Hydrogen glucose breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in irritable bowel syndrome.

BACKGROUND: Studies assessing the prevalence of small intestinal bacterial overgrowth in irritable bowel syndrome gave contrasting results. Differences in criteria to define irritable bowel syndrome patients and methods to assess small intestinal bacterial overgrowth may explain different results. Moreover, no data exist on small intestinal bacterial overgrowth prevalence in a significant population of healthy non-irritable bowel syndrome subjects. AIM: To assess the prevalence of small intestinal bacterial overgrowth by glucose breath test in patients with irritable bowel syndrome symptoms with respect to a consistent control group. METHODS: Consecutive patients with irritable bowel syndrome according to Rome II criteria were enrolled. The control population consisted of 102 sex- and age-matched healthy subjects without irritable bowel syndrome symptoms. All subjects underwent glucose breath test. A peak of H2 values >10 p.p.m above the basal value after 50 g of glucose ingestion was considered suggestive of small intestinal bacterial overgrowth. RESULTS: A total of 65 irritable bowel syndrome patients and 102 healthy controls were enrolled. Positivity to glucose breath test was found in 31% of irritable bowel syndrome patients with respect to 4% in the control group, the difference between groups resulting statistically significant (OR: 2.65; 95% CI: 3.5-33.7, P < 0.00001). CONCLUSIONS: The present case-control study showed an epidemiological association between irritable bowel syndrome and small intestinal bacterial overgrowth. Placebo-controlled small intestinal bacterial overgrowth-eradication studies are necessary to clarify the real impact of small intestinal bacterial overgrowth on irritable bowel syndrome symptoms.

Rifaximin dose-finding study for the treatment of small intestinal bacterial overgrowth.

BACKGROUND: Few controlled studies assessing choice and duration of antibiotic therapy for small intestinal bacterial overgrowth are available. AIM: To assess efficacy, safety and tolerability of different doses of rifaximin, a broad spectrum non-absorbable antibiotic, for intestinal bacterial overgrowth eradication. METHODS: We enrolled 90 consecutive patients affected by small intestinal bacterial overgrowth. The presence of small intestinal bacterial overgrowth was based on the occurrence of a rise of H2 values >12 p.p.m. above the basal value after 50 g glucose ingestion. Patients were randomized in three 7-day treatment groups: rifaximin 600 mg/day (group 1); rifaximin 800 mg/day (group 2) and rifaximin 1200 mg/day (group 3). Glucose breath test was reassessed 1 month after the end of therapy. Compliance to the treatment and incidence of side-effects were also evaluated. RESULTS: No drop-outs were observed in the three groups. Glucose breath test normalization rate was significantly higher in group 3 (60%) with respect to group 1 (17%; P < 0.001) and group 2 (27%, P < 0.01). No significant differences in patient compliance and incidence of side-effects were found among groups. CONCLUSIONS: Higher doses of rifaximin lead to a significant gain in terms of therapeutic efficacy in small intestinal bacterial overgrowth eradication without increasing the incidence of side-effects.

Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth and sugar malabsorption (lactose, fructose, sorbitol) may play a role in irritable bowel syndrome. The lactulose breath test is a reliable and non-invasive test for the diagnosis of small intestinal bacterial overgrowth. The lactose, fructose and sorbitol hydrogen breath tests are widely used to detect specific sugar malabsorption. AIM: To assess the extent to which small intestinal bacterial overgrowth may influence the results of hydrogen sugar breath tests in irritable bowel syndrome patients. METHODS: We enrolled 98 consecutive irritable bowel syndrome patients. All subjects underwent hydrogen lactulose, lactose, fructose and sorbitol hydrogen breath tests. Small intestinal bacterial overgrowth patients were treated with 1-week course of antibiotics. All tests were repeated 1 month after the end of therapy. RESULTS: A positive lactulose breath test was found in 64 of 98 (65%) subjects; these small intestinal bacterial overgrowth patients showed a significantly higher prevalence of positivity to the lactose breath test (P < 0.05), fructose breath test (P < 0.01) and sorbitol breath test (P < 0.01) when compared with the small intestinal bacterial overgrowth-negatives. Small intestinal bacterial overgrowth eradication, as confirmed by negative lactulose breath test, caused a significant reduction in lactose, fructose and sorbitol breath tests positivity (17% vs. 100%, 3% vs. 62%, and 10% vs. 71% respectively: P < 0.0001). CONCLUSIONS: In irritable bowel syndrome patients with small intestinal bacterial overgrowth, sugar breath tests may be falsely abnormal. Eradication of small intestinal bacterial overgrowth normalizes sugar breath tests in the majority of patients. Testing for small intestinal bacterial overgrowth should be performed before other sugar breath tests tests to avoid sugar malabsorption misdiagnosis.

How does human stem cell therapy influence gene expression after liver injury? Microarray evaluation on a rat model.

BACKGROUND: Tissue homeostasis is guaranteed by stem proliferating reserve, depending on dynamic changes in gene expression. A high plasticity is shown by the haematopoietic stem cells, potential source for liver regeneration. AIM: We aimed to evaluate the gene expression modifications induced by human haematopoietic stem cell therapy after liver injury in rats. SUBJECTS: Rats were sorted as follows: (A) human-haematopoietic stem cell injection after allyl alcohol liver damage; (B) only haematopoietic stem cell injection; (C) only allyl alcohol injection; and (D) sacrifice without any treatment. METHODS: Livers, spleens and bone marrows were analysed with flow-cytometry. Livers were also studied by reverse-transcription PCR, histology, immunohistochemistry and microarray analysis; selected genes were confirmed by real-time PCR. RESULTS: In subset A, haematopoietic stem cells were selectively recruited by liver, with respect to the group B, and they improved the liver regeneration process compared to group C. As regards microarrays, haematopoietic stem cell infusion upregulates 265 genes and downregulates 149 genes. Differentially regulated genes belong to a broad range of functional pathways, including proliferation, differentiation, adhesion/migration and transcripts related to oval-cell activation. Real-time PCR validated array results. CONCLUSIONS: Our study confirmed the capacity of haematopoietic stem cells to contribute to liver regeneration. Moreover, microarray analysis led to the identification of genes whose regulation strongly correlates with a more efficient process of liver repair after haematopoietic stem cell injection.

Helicobacter pylori infection and ischaemic heart disease: an overview of the general literature.

In the last years, a considerable number of studies have been performed on the correlation between Helicobacter pylori infection and ischaemic heart disease. The reason is the supposed role of some chronic infections in the genesis and development of vessel wall injury and atheromatous plaque, as already reported for Chlamydia pneumoniae and herpes viruses. While this association may be theoretically conceivable, it still remains debated from a practical point of view. Epidemiological and animal studies as well as some eradicating trials gave conflicting results, while studies investigating the specific molecular mimicry mechanisms induced by H. pylori strongly support the association. Moreover, none of the studies performed so far did take into account the effect of the genetic susceptibility to develop ischaemic heart disease or to respond to H. pylori infection. In particular, while the exposure to some known risk factor for atherosclerosis should lead to develop ischaemic heart disease, no condition or exposure, either individual or in combination, completely explains the occurrence and the progression of the disease, as many patients develop ischaemic heart disease in the absence of any risk factor. Based on these concepts, can we state that H. pylori infection may cause the same effect in patients with ischaemic heart disease as in healthy subjects? Further studies are needed in order to clarify this issue.

The decrease in cytokine concentration during albumin dialysis correlates with the prognosis of patients with acute on chronic liver failure.

BACKGROUND AND AIM: The clearance of plasma cytokines by means of albumin dialysis (MARS) has been demonstrated in various studies involving patients affected by either acute liver failure (ALF) or acute on chronic liver failure. The aim of the study was to measure the plasma levels of TNF-alpha, IL-6, and IL-1beta in patients with ALF after each MARS treatment to evaluate the relationship between variations in cytokines levels and patient prognosis. MATERIALS AND METHODS: Ten patients with ALF undergoing several MARS treatments were enrolled (group 1). Blood samples were collected before and after each MARS treatment to measure TNF-alpha, IL-6, and IL-1beta, and other hematochemical parameters. We also enrolled 10 patients with ALF who underwent standard therapy (group 2) as well as a control group of 10 healthy subjects matched for sex and age (group 3). RESULTS: MARS reduced total bilirubin levels, biliary acids, BUN, ammonia, TNF-alpha, IL-6, and IL-1beta (P < .05). Moreover, the reduction in inflammatory cytokines levels and improved prognosis were related. CONCLUSIONS: We confirmed the therapeutic efficacy of MARS treatment for ALF, which appeared to be related to removal of toxins and inflammatory cytokines determine that which patients prognosis.

Hepatic steatosis and vascular disease.

Nonalcoholic fatty liver disease (NAFLD) refers to a wide picture of liver damage, ranging from steatosis to steatohepatitis, fibrosis and cirrhosis. The epidemiological studies demonstrated an association of NAFLD with obesity, type 2 diabetes and hyperlipidemia. Under this light the metabolic syndrome (MS), including NAFLD, obesity, central fat distribution, diabetes, dyslipidemia, hypertension and atherosclerotic cardiovascular disease (CVD) can be considered the link to explain the presence of vascular diseases in patients with NAFLD. In NHANES III, the authors demonstrated that the presence of MS was associated with increased risk of myocardial infarction, stroke or both. In a prospective study on 1209 Finnish middle-aged men without CVD or diabetes at baseline, Lakka showed that MS per se is associated with an increased risk of CVD and all-cause mortality. Finally the Atherosclerosis Risk in Communities (ARIC) confirmed that subjects with MS were 2 times more likely to have prevalent coronary heart disease. From a pathophysiological point of view, growing evidences implicate the oxidative stress as the unifying mechanism for many CVD risk factors. Under this light there is emerging evidence suggesting that there is a significant increase in vascular oxidative stress in patients with MS, with the presence of endothelial dysfunction in the early stage of the syndrome. Indeed, the inflammation process evidentiated in these patients is initiated at the endothelial level, stressing the key role of this active and dynamic tissue in the pathophysiological pathways. Under this light the endothelium can be considered as the last effector of a multi-syndrome and the main target of all the future studies focused on the underlying mechamisms of this complex network. Because of the potential serious public health impact, the comprehension of these patophysiological pathways will be crucial to design new preventive measures and therapeutic strategies.

Improvement of mitochondrial function evaluated by ketoisocaproic acid breath test in patients with HCV infection undergoing albumin dialysis.

BACKGROUND AND AIM: Oxidative injury occurs as a direct result of hepatitis C virus (HCV) core protein expression both in vitro and in vivo, and may be due to a direct effect on mitochondria. The ketoisocaproic acid (KICA) breath test is a simple, reliable, and noninvasive test to evaluate hepatic mitochondrial function. Albumin dialysis (MARS) is an effective bridge treatment for patients with acute failure superimposed on chronic liver disease. The aim of our study was to evaluate the improvement of mitochondrial function measured by KICA in patients undergoing MARS for acute-on-chronic HCV liver failure. MATERIALS AND METHODS: Five patients with HCV chronic infection undergoing MARS treatment for acute decompensation were enrolled. Before and after each MARS treatment, patients underwent blood testing for the main hematochemical parameters as well as for mitochondrial function by the KICA breath test and the arterial ketone bodies ratio (AKBR). RESULTS: MARS treatment effectively decreased the serum level of total bilirubin, bile acids, urea, and ammonium. Moreover, MARS treatment produced an increase in AKBR and in the cumulative percentage of (13)CO(2) recovered in exhaled air 2 hours after KICA ingestion. CONCLUSION: Liver mitochondrial function appears to be beneficially affected by MARS treatment.

No evidence of hematopoietic stem cell mobilization in patients submitted to hepatectomy or in patients with acute on chronic liver failure.

BACKGROUND: Liver regeneration is a heterogeneous phenomenon involving the proliferation of different cell lineages in response to injury. Under a strong positive selection pressure bone marrow derived stem cells may be involved in this process, by making a contribution to both parenchymal restoration and endothelial cell replacement. We investigate bone marrow stem cell migration to the liver in patients undergoing hepatectomy or with acute on chronic liver failure. METHODS: We enrolled 6 patients submitted to hepatectomy, 6 patients to cholecystectomy and 8 patients with acute decompensation of liver cirrhosis. Mobilization of CD34+ cells was evaluated by cytofluorimetry on peripheral blood samples at different time points; baseline, 1, 3, 7, 15 and 30 days after surgery and at admission, 1, 7 and discharge among patients with acute on chronic liver failure. 10 healthy subjects undergoing blood donation were also enrolled to evaluated the basal value of CD34+ cells. RESULTS: White blood cell counts remained in the normal range (4.1-9.8 x 10(9)/L) in all groups throughout the follow-up. In all patients of Groups 1, 2 and 3, circulating CD34+ failed to show statistically significant differences both as the absolute number and as the percentage at any time point compared to healthy controls. CONCLUSIONS: Bone marrow derived cell mobilization can not be detected after hepatectomy or during an acute decompensation on a cirrhotic liver. Under these circumstances liver regeneration can probably call upon mature hepatocytes and endogenous progenitor cells. The involvement of extrahepatic progenitors if any, is a rare and limited phenomenon.

Transdifferentiation of stem cells in pancreatic cells: state of the art.

Among the different approaches for diabetes mellitus-pancreas and pancreatic islet transplantation-the use of stem cells represent a renewable alternative source of insulin-producing cells. Stem cells capable of differentiating into beta-like cells can be isolated namely from embryonic cells, bone marrow, and umbilical cord blood, but also from adult organs such as pancreas, liver, and spleen. Several studies have demonstrated that by manipulating culture conditions and using growth and transcription factors of beta-cell lineage (in particular pdx-1 and pax4), embryonic stem cells can differentiate in vitro after formation of embryoid bodies. Bone marrow stem cells can give rise to mesenchymal; endodermal-, and ectodermal-derived cells. In vivo it has been shown that after bone marrow transplantation, using a murine sex-mismatched model, insulin-producing cells expressing the Y chromosome can be detected in the donor pancreas, although not in a significantly number. Cells characterized by a group of markers (Nestin, CK-8, CK-18) and transcription factors (Isl-1, Pdx-1, Pax-4, Ngn-3) important for beta-cell differentiation have been detected in umbilical cord blood. The recent evidence of the possibility to transdifferentiate stem cells to beta cells encourages further studies in animal models to exhaustively determine the differentiation pathways of stem cells to insulin producing cells. These findings might open the way to a successful human investigation.

Improvement of mortality rate and decrease in histologic hepatic injury after human cord blood stem cell infusion in a murine model of hepatotoxicity.

BACKGROUND AND AIMS: Because of their plasticity potential local and systemic application of cord blood stem cells may represent excellent candidates for cell-based therapeutic strategies in toxic liver injuries. It is already known that intraperitoneal administration of hematopoietic stem cells provides rapid liver homing in animal models of hepatic injury. We sought to assess the efficacy of a hematopoietic stem cell infusion to decrease the histologic damage and the mortality rate of animals previously damaged by allyl alcohol. MATERIAL AND METHODS: NOD/SCID mice were divided into two groups. (1) animals treated by intraperitoneal administration of allyl alcohol and (2) animals treated with allyl alcohol and 24 hours later with an intraperitoneal infusion of human cord blood cells. Flow cytometry, histology, immunohistochemistry, and RT-PCR were performed to monitor human cell engraftment by evidences of human hepatic markers. RESULTS: Human stem cells were able to transdifferentiate into hepatocytes, improve liver regeneration after damage, and reduce the mortality rate even when requiring qualitative and quantitative differences in the transdifferentiation processes. The mortality rate decreased from 70% to 20%, with a significant improvement in the histologic findings. CONCLUSION: We demonstrated that the infusion of hematopoietic stem cells into the liver in the early stage of damage might initiate endogenous hepatic tissue regeneration that oppose the injury inflicted by toxicants.

Catholic university experience with molecular adsorbent recycling system in patients with severe liver failure.

BACKGROUND AND AIM: Molecular adsorbent recycling system (MARS) treatment is able to remove both hydrosoluble and small- and medium-sized lipophilic toxins. MARS plays an important role in modifying liver failure complications, such as hepatorenal syndrome and hepatic encephalopathy. We sought to evaluate the clinical efficacy and safety of a MARS device in a consecutive series of hepatic failure patients. MATERIALS: Twenty patients with acute liver failure, transplantation failure, or acute on chronic liver failure fulfilled the inclusion criteria of total bilirubin > or =10 mg/dL and at least one of the following: hepatic encephalopathy (HE) > or =II grade, hepatorenal syndrome (HRS) for chronic patients or total bilirubin > or =5 mg/dL and HE > or =I grade for acute patients. RESULTS: MARS was able to reduce cholestatic parameters and improve neurologic status and renal function parameters in all treated patients. We also observed an improvement in the 3-month survival rate compared to the expected outcome in patients with MELD scores between 20 and 29, as well as 30 and 39. CONCLUSIONS: Based on these results, we confirm the safety and clinical efficacy of MARS treatment, with the best results in patients with MELD score of 20 to 29. Further studies are necessary to confirm whether this treatment is able to modify patient outcomes and prognosis.

Human cordonal stem cell intraperitoneal injection can represent a rescue therapy after an acute hepatic damage in immunocompetent rats.

BACKGROUND AND AIM: Tissue homeostasis and turnover require reserve stem proliferating cells. Several studies performed on immunodeficient animals have suggested a degree of plasticity by the hematopoietic stem cell compartment that may represent source for liver regeneration. We sought to explore the hepatic differentiation potential of hematopoietic stem cells from human cord blood, after toxic liver damage induced by allyl-alcohol in immunocompetent rats. MATERIALS AND METHODS: Wistar rats were divided into groups (A) allyl-alcohol intraperitoneal injection with hematopoietic stem cell intraperitoneal infusion at 1 day and sacrifice 3 days later; (B) stem cell injection and sacrifice 3 days later; (C) allyl-alcohol infusion and sacrifice 4 days later; and (D) sacrifice without any treatment. Livers, spleens, and bone marrows were analysed for human stem cells using flow-cytometry; livers were also tested by histology and immunohistochemistry to study the pattern of hepatic regeneration after damage and human stem cell conversion into hepatocyte-like cells, respectively. RESULTS: Flow-cytometry revealed selective recruitment of human hematopoietic stem cells by damaged livers (group A) compared with control group B. In addition, liver damage was reduced in animals treated with stem cells. Immunohistochemistry demonstrated that human stem cells could convert hepatic cells. CONCLUSIONS: Our study demonstrated that hematopoietic stem cells selectively recruited by injured livers can contribute to hepatic regeneration after acute toxic damage in immunocompetent recipients.

Intermittent anoxia reduces oxygen free radicals formation during reoxygenation in rat hepatocytes.

The sensitivity of liver cells to anoxia is a major problem afflicting liver preservation and transplantation. Intermittent ischemia has been proposed to reduce reperfusion injury. The aim of the study was to assess oxygen free radical formation and cell injury during continuous or intermittent anoxia/reoxygenation in rat hepatocytes. Anion superoxide was measured by lucigenin-enhanced chemiluminescence and cell damage by LDH release and trypan blue uptake. During anoxia, superoxide generation dropped to background level in both groups; trypan blue uptake and LDH release, which increased progressively, were significantly greater in hepatocytes exposed to continuous compared to intermittent anoxia. During reoxygenation, a massive generation of superoxide anion formation, followed by a sharp increase in LDH release, was observed in both groups. However, both oxyradical generation and cell injury were significantly greater in cells exposed to continuous compared to intermittent anoxia. The data, showing that intermittent oxygen deprivation reduce liver cell injury and oxygen free radical formation determined by anoxia/reoxygenation, suggest a novel possible approach to the reduction of reperfusion injury.

Fibrinogenemia, determined immunonephelometrically, as a possible parameter in the evaluation of peripheral arteriosclerotic arteriopathy.

The concentration of plasma fibrinogen increases with age and is particularly elevated in subjects with vascular changes due to atherosclerosis. Fibrinogen, which is the meeting point of the "cascade" of the coagulation factors and an important regulating factor of plasma viscosity, occupies a key position in atherosclerotic vascular pathology. This indicates the necessity to keep its value within normal limits, to avoid the clinical development of the disease or improve its evolution. Thus, frequent checks of the fibrinogenemia are necessary at various ages even if this means a big organizational burden. However, this checking can be facilitated by using automatic techniques, such as the immunonephelometric method, with which it is possible to carry out a large number of determinations in a short time.

Replacement therapy with a purified protein C concentrate during initiation of oral anticoagulation in severe protein C congenital deficiency.

The case of an adult patient with moderately severe protein C deficiency (antigen 16%, activity 12%) is reported. Both parents had protein C levels compatible with heterozygous deficiency. Unlike other reported cases of severe protein C deficiency in adults, the onset of thrombotic symptoms occurred at 1 month of age; however, a symptom-free period until age 17 followed. Replacement therapy with a monoclonal antibody purified protein C concentrate was carried out during the initiation of oral anticoagulation after a course of i.v. heparin for deep vein thrombosis. The administration of the concentrate allowed maintenance of protein C above 50% until a stable therapeutic anticoagulation level could be obtained. This was reached within a short time, thus allowing safe administration of a loading dose of warfarin. We conclude that this approach to the prevention of skin necrosis seems more rapid and safer than previous schedules of oral anticoagulation in protein C-deficient patients.