OBJECTIVE: To describe the efficacy and safety of protein C (PC) concentrate to restore physiological values in adult septic patients having clinical contraindications to activated PC. DESIGN: Case series (pilot study). SETTING: Three adult ICUs of a University Hospital. PATIENTS AND PARTICIPANTS: Twenty adult patients affected by severe sepsis or ...

BACKGROUND: Recombinant activated factor VII (rFVIIa) is a hemostatic agent developed for the treatment of bleeds in patients with hemophilia and inhibitors. Case reports/series document its growing use in patients without hemophilia. Such reports however do not accurately describe the proportion of rFVIIa used for various indications. We sought to ...

Many coagulation abnormalities are known to coexist in patients with AL amyloidosis; however, disseminated intravascular coagulation (DIC) is rarely observed. We describe the case of a 61-year-old woman who presented with systemic purpura, macroscopic hematuria, and hepatosplenomegaly as the initial manifestations of systemic AL amyloidosis. A coagulation study revealed severe ...

Monitoring of the global haemostatic capacity is desired to optimize the treatment with bypassing agents in inhibitor patients. Thrombelastographic methods have been used in ex vivo studies and were suggested useful to evaluate the individual response to bypassing agents. This study aimed at assessing changes in thrombelastographic profiles and their ...

Patients with congenital heart disease (CHD) often do have a variety of coagulation abnormalities that results in bleeding diathesis. Our study aimed to determine the impact of cyanosis and CHD on modified thrombelastography parameters, compared with children without CHD. Preoperative blood samples were taken for TEM analyses from a total ...

Recombinant activated factor VII (rFVIIa; NovoSeven, NiaStase, Novo Nordisk, Bagsvaerd, Denmark) was originally developed for the treatment of bleeds in patients with hemophilia and inhibitors. However, the agent is increasingly being employed in "off-label"/unlicensed indications. Consequently there is a need to undertake comprehensive reviews of rFVIIa use; the resulting information ...

BACKGROUND: Plasminogen activator inhibitor 1 (PAI-1) attenuates the conversion of plasminogen to plasmin. Polymorphisms of the PAI-1 gene are associated with varying PAI-1 levels and risk of prothrombotic events in nonsurgical patients. The purpose of this study, a secondary analysis of a clinical trial, was to investigate whether PAI-1 genotype ...

Angioedema manifests as episodes of localized swelling in the dermis and submucosa. The key to successful management is detection and avoidance of triggers, early recognition of attacks, and aggressive airway management when warranted. Review of a patient's medication list may identify drugs that include angiotensin-converting enzyme inhibitor or angiotensin receptor ...

The inhibitor titer is the most important clinical measurement in inhibitor patients, and the Nijmegen method is preferable to the original and well-established Bethesda assay for this purpose; however, both methods have high inter-laboratory variability. Monitoring inhibitor patients after treatment with bypassing agents is difficult. Treatment with recombinant activated factor ...

The decreased survival of von Willebrand factor (VWF) in plasma has been implicated as a mechanism in a subset of type 1 von Willebrand disease (VWD) patients. We have previously reported that the ratio of plasma levels of VWF and its propeptide (VWFpp) can be used to identify patients with ...

BACKGROUND: An increased incidence of thromboembolic events has been described in patients with cancer. Cancer cells are attributed with producing procoagulant substances such as cysteine protease and tissue factor to activate factor X and factor VII, respectively. However, there are limited data on the pathogenesis behind this hypercoagulability state, and ...

BACKGROUND: Epistaxis is a common emergency in otolaryngology. There is some evidence questioning the use of routine coagulation studies (prothrombin time and activated partial thromboplastin time (APTT)) in these patients, but this practice continues in most centres. AIM: To identify groups of patients likely to present with coagulation abnormalities. METHODS: ...

Constitutively overproduced in proliferating synovial tissues, interleukin-6 (IL-6) is deeply involved in the pathology of rheumatoid arthritis (RA). Tocilizumab is a humanized anti-human IL-6 receptor antibody that binds to soluble and membrane-bound IL-6 receptor, and at detectable levels in blood, tocilizumab is capable of almost completely blocking the transmembrane signaling ...

OBJECTIVE: Outcomes after ventricular assist device (VAD) implantation have significantly improved during the last decade. However, bleeding episodes remain a serious complication of VAD support. This cannot be explained by the individual anticoagulation regimen alone in several cases, but may be symptomatic of acquired von Willebrand disease (VWD). The leading ...

Hereditary angioedema is an episodic swelling disorder with autosomal dominant inheritance. Attacks are characterized by brawny, self-limited, nonpruritic edema of the deep dermal layers of the skin that most often involve the hands and feet. They usually begin in childhood and become more severe after puberty. Patients also have episodic ...

It has been long recognized that 10 to 15% of patients with "phenotypically characterized" severe hemophilia (< 1% clotting factor activity) have relatively mild disease clinically. Not all these patients have frequent spontaneous bleeding, and even among those who bleed, the extent of joint damage tends to vary considerably. The ...

PROBLEM: Placental fibrin deposits in patients wih recurrent spontaneous abortion (RSA) indicate an exaggerated haemostatic response. This 'hypercoagulability' may involve pro-coagulant factors such as circulating microparticles (MPs). We investigated the relationship between circulating pro-coagulant MPs and systemic coagulation in RSA patients. METHOD OF STUDY: Platelet- and endothelial cell-derived microparticles (PMPs, ...

We have prospectively evaluated the biologic response to desmopressin in 77 patients with type 1 von Willebrand disease (VWD) enrolled within the Molecular and Clinical Markers for the Diagnosis and Management of type 1 VWD project. Complete response to desmopressin was defined as an increase of both ristocetin cofactor activity ...

BACKGROUND: Diagnosis of acquired von Willebrand syndrome (AVWS) remains challenging. Diagnostic algorithms suggest the use of factor VIII (FVIII:C), von Willebrand factor antigen (VWF:Ag), ristocetin cofactor (VWF:RCo), and collagen-binding capacity (VWF:CB), but the sensitivity of these and other laboratory tests for the diagnosis of AVWS is unknown. Objectives: To analyze ...

BACKGROUND: Disseminated intravascular coagulation (DIC) is common among patients with sepsis. Leptospirosis is an important cause of sepsis in tropical areas, and pulmonary hemorrhage associated with thrombocytopenia is the major cause of death, but the coagulopathy in severe leptospirosis has not been further characterized. The aim of this study was ...

The introduction of new factor concentrates has, at times, resulted in an increase in inhibitor development; hence large systematic surveys of inhibitor development are necessary whenever new products are introduced. This study presents the results of a surveillance study conducted by the Inhibitor Subcommittee of the Association of Hemophilia Clinic ...

Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor VII or eptacog alfa) is structurally similar to human plasma-derived coagulation factor VIIa, but is manufactured using DNA biotechnology. Recombinant factor VIIa interacts with thrombin-activated platelets to produce a thrombin burst leading to accelerated fibrin clot formation localized to the ...

BACKGROUND: Previous studies have shown that patients with multiple-drug allergy syndrome (MDAS) frequently have positive autologous serum skin test results, similar to patients with chronic urticaria (CU). Recent investigations have found that patients with CU show signs of thrombin generation and activation of the tissue factor pathway of the coagulation ...

The synthetic vasopressin analogue (1-deamino-8-D-arginine-vasopressin) increases plasma concentration of factor VIII and von Willebrand factor in normal subjects and patients with mild haemophilia A and von Willebrand disease. Since its first clinical use in 1977, desmopressin has become the treatment of choice for patients with haemophilia A and factor VIII ...

PURPOSE: To determine the prevalence of prior or current usage of COX-2 inhibitors among patients with retinal venous occlusion (RVO). METHODS: Records of all patients with RVO and control patients matched by age and gender without the diagnosis of RVO seen in a retina referral practice between May 1999 and ...

INTRODUCTION: The aim of the present study was to establish whether the presence of chronic viral hepatitis (PVH) could be implicated in the elevation of oxidative stress (SOX) and haemostasis system in haemodialysis (HD) patients. MATERIALS AND METHODS: In HD patients with and without PVH and in controls we compared ...

BACKGROUND: Pulmonary hypertension (PHT) is common in sickle cell disease (SCD). The purpose of this study was to determine whether markers of coagulation activation and inflammation are associated with PHT in SCD. DESIGN AND METHODS: This cross-sectional study was performed using a cohort of patients followed at an adult Sickle ...

Prothrombin time (PT) is the leading test for monitoring oral anticoagulation therapy (OAT). We sought to determine INR taking into account only active coagulation factors FII, FVII and FX without inhibition in patient plasmas and calibrator kits.We measured PT using a combined thromboplastin reagent. The calculation was based on a ...

OBJECTIVE: Thrombosis has been widely described after the Fontan procedure. The vascular endothelium plays a central role in the control of coagulation and fibrinolysis. The aim of this study was to investigate if patients undergoing a modified Fontan procedure have impaired endothelial function and fibrinolysis in the late postoperative course. ...

Glanzmann thrombasthenia (GT) is a rare platelet function disorder characterized by a defect in fibrinogen binding to platelet membrane glycoprotein (GP) IIb/IIIa. Recombinant FVIIa (rFVIIa) is a haemostatic agent approved for the treatment of haemophilia patients with inhibitors, patients with acquired haemophilia and in EU also for treatment of factor ...

The incidence of inhibitors in haemophilia A is 21-33%. The development of inhibitors to factor VIII (FVIII) is one of the most serious complications in haemophilia therapy and is an important challenge in haemophilia care. The main short-term objective of the treatment of haemophilic patients with inhibitors is to control ...

This retrospective survey of haemophilia A patients from multiple treatment centres in Ireland assessed the development of inhibitors following a switch in the prescribed treatment from recombinant factor VIII (rFVIII) produced by Chinese hamster ovary (CHO) cells (rFVIII-CHO) to rFVIII produced by baby hamster kidney (BHK) cells (rFVIII-BHK). Ninety-four patients ...

Venous thromboembolism (VTE) has been reported to be less common among Thais than Caucasians. Whether this observation reflects genetic or environmental factors, or both, is uncertain. To identify genetic and acquired risk factors of Thai patients with VTE, we enrolled in the study 105 consecutive Thai patients (34 men, 71 ...

BACKGROUND AND OBJECTIVES: In pediatric meningococcal sepsis, an imbalance between coagulation and fibrinolysis and proinflammatory action play major roles. We hypothesized that thrombin activatable fibrinolysis inhibitor (TAFI) and/or TAFI activation markers are involved in the pathogenesis of meningococcal sepsis. PATIENTS AND METHODS: Children with severe meningococcal sepsis (n = 112) ...

Thromboelastography (TEG) assesses the global pattern of blood coagulation in the whole blood. Present day management of haemophilia is based on replacement therapy with lost factor by parenteral administration of factor concentrates. It is very well known that interaction of cellular components in the blood also affect the thrombin generation ...

This article describes a 4-y-old girl with spontaneous, generalized bruising, abdominal distention, and signs of malnutrition. She had been treated previously with an antibiotic for diarrhea. Laboratory analyses showed the presence of iron-deficiency anemia, mild hypoalbuminemia, and considerably prolonged prothrombin time and activated thromboplastin time. Tests revealed that hemostasis improved ...

During the past few decades, great progress has been made toward a better understanding of the development of the hemostatic system. It is now clear that the physiology of hemostasis in pediatric patients differs widely from that in adults, supporting the hypothesis that children might have natural protective mechanisms that ...

PURPOSE: A new type of hereditary angioedema was described recently. It was characterized by recurrent bouts of angioedema in various organs and normal C1 inhibitor and was observed mainly in women. Our aim was to conduct a detailed study of the clinical features of this condition. METHODS: A total of ...

BACKGROUND: Severe FX deficiency is a rare disorder with a variable bleeding tendency but spontaneous life threatening haemorrhage can occur. Treatment for invasive procedures and spontaneous bleeding is with prothrombin complex concentrates (PCC). When used in large or repetitive doses these are associated with a thrombotic tendency. FX:C levels of ...

Factor VIII (FVIII) inhibitors remain a serious complication of treatment for patients with haemophilia A. Immune tolerance induction (ITI) can eliminate inhibitors in the majority of patients, but there are major concerns related with this therapy. Investigators have raised the possibility that the use of FVIII/von Willebrand factor (FVIII/VWF) concentrates ...

BACKGROUND: Acute coronary syndrome (ACS) is associated with thrombin formation, triggered by ruptured or eroded coronary atheroma. We investigated whether thrombin generation based on circulating coagulation protein levels, could distinguish between acute and stable coronary artery disease (CAD). METHODS AND RESULTS: Plasma coagulation factor (F) compositions from 28 patients with ...

BACKGROUND: Melioidosis, which is caused by infection with the Gram-negative bacterium Burkholderia pseudomallei, is an important cause of sepsis in South-East Asia with a mortality of up to 40%. Knowledge of the involvement of coagulation and fibrinolysis in the pathogenesis of melioidosis is highly limited. OBJECTIVE: To define the involvement ...

BACKGROUND: A ruptured abdominal aortic aneurysm (AAA) is associated with high mortality. Postoperative complications such as hemorrhage, multiple organ failure, myocardial infarction, and thromboembolism are common. An active and balanced hemostatic system is essential to avoid bleeding as well as thrombosis. When these activities are not properly regulated the patient ...

Hemophilia A is a sex-linked hereditary disease, and the total number of patients with this condition is small. It is quite rare for general surgeons to encounter a patient with hemophilia A. Moreover, it is extremely rare for surgeons to encounter adult patients with undiagnosed hemophilia. We describe a patient ...

Acquired hemophilia is an unusual disorder in which nonhemophiliac patients develop autoantibodies (inhibitor) against the factor VIII coagulation protein. Factor VIII inhibitor leads to life-threatening bleeding disorders classically described as new onset of diffuse bruising and prolonged partial thromboplastin time in elderly patients. Treatment is focused in the control of ...

Fifty-three patients of thalassemia intermedia and 40 controls were studied for clinical evidence of thrombosis and laboratory evidence of hypercoagulable state. Thrombotic episodes were detected in 5 (9.4%) patients. Two of these 5 patients with thrombosis were splenectomized. Laboratory evaluation showed presence of thrombocytosis in 8 (15%), 5 of these ...

Thrombophilia is considered to increase the risk of venous thrombosis (VT) due to hemostasis activation. To determine the level of hemostasis activation in thrombophilic subjects with or without a history of VT, hemostasis activation markers prothrombin fragment 1 and 2 (F1+2), thrombin-antithrombin complex (TAT), and cross-linked fibrin degradation products (D-dimer) ...

Thrombotic thrombocytopenic purpura (TTP) is a rare disease which responds well to plasma exchange treatment in the majority of patients. We report on a patient with acute TTP caused by severe autoantibody-mediated ADAMTS-13 deficiency, in whom remission was not achieved by initial treatment consisting of plasma exchange (PE), plasma infusion ...

The plasma levels of D-dimer can be used as a marker of fibrin formation and degradation. Plasma D-dimer levels in the febrile phase of 6 patients with typhoid fever and in the afebrile convalescent phase of 4 of them were measured. D-dimer levels were high in the febrile phase of ...

Recombinant activated factor VII has been Food and Drug Administration approved to treat hemorrhages in hemophiliac patients with inhibitors and in acquired hemophilia patients. Recombinant activated factor VII use has also been considered for the management of uncontrolled bleeding in a number of congenital and acquired hemostatic abnormalities. The myeloproliferative ...