Application of a clinical decision rule and laboratory assays in pediatrics: Adult heparin-induced thrombocytopenia.

Background: Heparin-induced thrombocytopenia (HIT) is rare among pediatric patients. The diagnosis of HIT depends upon clinical decision tools to assess its pretest probability, supported by laboratory evidence of anti-platelet factor 4 (anti-PF4)/heparin antibodies.

Aims: To compare the use of the 4Ts score clinical decision tool, clinical characteristics, and laboratory findings between pediatric and adult patients with suspected HIT.

Rivaroxaban treatment among children with cancer-associated thromboembolism: Real-world data.

This is the first study examining real-life data of pediatric cancer patients treated with rivaroxaban. Children with thrombocytopenia and high bleeding risk were excluded from previous clinical trials. Data regarding the safety and efficacy of rivaroxaban in pediatric cancer-associated thrombosis are scarce.

The potential role of emicizumab prophylaxis in severe von Willebrand disease.

Background: Severe von Willebrand disease (VWD) may be associated with chronic joint damage and may require prophylactic therapy. Emicizumab is a humanized bispecific antibody, which mimics the function of coagulation factor VIII (FVIII), and it has been approved for prophylaxis in hemophilia A.

Methods: This is the first study assessing the potential future role of emicizumab as an alternative prophylactic treatment in patients with severe VWD, based upon a thrombin generation (TG) ex vivo analysis.

Emicizumab treatment and monitoring in a paediatric cohort: real-world data.

Real-world data on emicizumab use and monitoring in paediatric severe haemophilia A (HA) patients are scarce. We therefore sought to evaluate safety, efficacy, and laboratory monitoring of emicizumab prophylaxis in a cohort of 40 children with severe HA, including 22 non-inhibitor patients and nine infants younger than one year. Bleeding, trauma, adverse events, and surgeries were documented during a median follow-up of 45 weeks.

Safety of cataract surgery in patients treated with the new oral anticoagulants (NOACs).

Purpose: To evaluate the safety of phacoemulsification of cataract in patients taking new oral anticoagulants (NOACs).

Methods: In a prospective case series, consecutive patients on NOACs (dabigatran, rivaroxaban, or apixaban) who were referred for uncomplicated cataract surgery to the eye institute underwent a thorough ophthalmological and hematological evaluation. Rivaroxaban and apixaban anti-factor Xa tests, and diluted thrombin time for dabigatran, were used for monitoring anticoagulation levels in blood.

Single Low Dose of rFVIIa Combined with Antifibrinolytic Agent is a Simple and Safe Treatment for Factor XI-Deficient Patients undergoing Surgery.

Background:  Factor XI (FXI) deficiency is a rare autosomal bleeding disorder. The rarity of spontaneous bleeding and absence of optimal tools to predict the bleeding risk in FXI-deficient patients hamper the standardization of prophylactic treatment enabling them to undergo major surgeries without blood products.

Objectives:  We explored the effectiveness of a single and very low dose of recombinant factor VIIa (rFVIIa) along with tranexamic acid (TXA) as prophylactic treatment for FXI-deficient patients undergoing various types of surgery at various sites of injury.

A Novel Compound Targeting Protease Receptor 1 Activators for the Treatment of Glioblastoma.

Data from human biopsies, and models, strongly supports the role of thrombin, and its protease-activated receptor (PAR1) in the pathology and progression of glioblastoma (GBM), a high-grade glial tumor. Activation of PAR1 by thrombin stimulates vasogenic edema, tumor adhesion and tumor growth. We here present a novel six amino acid chloromethyl-ketone compound (SIXAC) which specifically inhibits PAR1 proteolytic activation and counteracts the over-activation of PAR1 by tumor generated thrombin.

The Organophosphate Paraoxon and Its Antidote Obidoxime Inhibit Thrombin Activity and Affect Coagulation In Vitro.

Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as thrombin and on coagulation tests have been only partially characterized and potential interactions with OPs antidotes such as oximes and muscarinic blockers have not been addressed. In the current study, we investigated the in vitro interactions between coagulation, thrombin, the OP paraoxon, and its antidotes obidoxime and atropine.

Thromboelastography during coronary artery bypass grafting surgery of severe hemophilia A patient - the effect of heparin and protamine on factor VIII activity.

: Coronary artery bypass grafting surgery (CABG) in hemophilia patients is challenging. Thromboelastography (TEG) is useful to assess hemostasis perioperatively. A patient with severe hemophilia A underwent CABG with TEG studies.

Factor XI Deficiency Protects Against Atherogenesis in Apolipoprotein E/Factor XI Double Knockout Mice.

Objective: Atherosclerosis and atherothrombosis are still major causes of mortality in the Western world, even after the widespread use of cholesterol-lowering medications. Recently, an association between local thrombin generation and atherosclerotic burden has been reported. Here, we studied the role of factor XI (FXI) deficiency in the process of atherosclerosis in mice.

Assessment of Functional Fibrinolysis in Cord Blood Using Modified Thromboelastography.

Background: The fibrinolytic system in newborns is immature and probably impaired. The aim of this study was to prospectively evaluate functional fibrinolytic capacity of newborn's cord blood using a new thromboelastometry (rotational thromboelastogram, ROTEM®) test.

Methods: Infants born at Sheba Medical Center were studied prospectively.

The impact of thrombin generation and rotation thromboelastometry on assessment of severity of factor XI deficiency.

The phenotype of bleeding in patients with severe FXI deficiency is unpredictable and unlike other bleeding disorders, it is not directly correlated with levels of FXI. In this study we analyzed whether the global coagulation assays can serve as a clinical tool in predicting bleeding tendency in patients with severe FXI deficiency undergoing surgery, taking into account the large inter-individual variability of FXI levels and genotypes. Thrombin generation (TG) was measured in 39 platelet-poor plasma with or without tissue factor (TF) and in the presence or absence of corn trypsin inhibitor (CTI).

Plasma tissue-type plasminogen activator increases fibrinolytic activity of exogenous urokinase-type plasminogen activator.

The relationship between tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) function is not fully understood. The aim of this study was to compare in vitro the fibrinolytic activity of tPA and uPA and evaluate their possible interaction. Blood coagulation and fibrinolysis were conducted by rotation thromboelastometry, whereas blood clotting was induced by CaCl2 and tissue factor and fibrinolysis additively by tPA and uPA.

Recombinant factor VIIa treatment for asymptomatic factor VII deficient patients going through major surgery.

Factor VII deficiency is the most common among the rare autosomal recessive coagulation disorders worldwide. In factor VII deficient patients, the severity and clinical manifestations cannot be reliably determined by factor VII levels. Severe bleeding tends to occur in individuals with factor VII activity levels of 2% or less of normal.

The in-vitro effect of fibrinogen, factor XIII and thrombin-activatable fibrinolysis inhibitor on clot formation and susceptibility to tissue plasminogen activator-induced fibrinolysis in hemodilution model.

Patients suffering major traumatic or surgical bleeding are often exposed to hemodilution resulting in dilutional coagulopathy. The aim of this study was to evaluate in vitro the effects of fibrinogen, factor XIII and thrombin-activatable fibrinolysis inhibitor (TAFI) on clot formation and resistance to fibrinolysis in hemodilution conditions. Citrated whole blood from 36 healthy volunteers was diluted to 30 and 60% with lactated Ringer's solution.

Severe factor X deficiency in three unrelated Palestinian patients is caused by homozygosity for the mutation c302delG-correlation with thrombin generation and thromboelastometry.

Factor X (FX) is one of the vitamin K-dependent serine proteases, which forms the prothrombinase complex converting prothrombin into thrombin. To search for mutations in F10 gene giving rise to severe FX deficiency and to study the contribution of thrombin generation and thromboelastometry as a tool for evaluation of hemostasis. Mutations in the F10 gene were sought by direct sequencing of all the eight exons and intron/exon boundaries.

Point of care testing in children undergoing cardiopulmonary bypass.

Background: Excessive hemorrhage is a major complication after cardiac surgery requiring cardiopulmonary bypass (CPB). The aim of this study was to define the potential role of the cone and platelet analyzer (CPA) and the rotating thromboelastogram (ROTEM) point of care tests in children undergoing CPB.

Procedure: We prospectively studied 15 pediatric patients aged 1 month to 10 years.

Thrombin generation assay as a possible tool for assessment of reduced activity of clotting factors induced by antiphospholipid antibodies and in-vitro evaluation of treatment options.

Bleeding is a rare manifestation of antiphospholipid syndrome, unless associated with reduced clotting factors or severe thrombocytopenia. Accurate assessment of the autoantibodies in plasma is very important since the autoantibodies can lead to bleeding or thrombosis. The objective of the present study was to define the inhibitors causing reduced clotting activity in a patient with antiphospholipids antibodies and to assess the potential of thrombin generation assay to assist in establishment of optimal treatment in case of major bleeding.

Recombinant activated factor VII and tranexamic acid are haemostatically effective during major surgery in factor XI-deficient patients with inhibitor antibodies.

One-third of patients with severe factor XI (FXI) deficiency caused by homozygosity for null alleles develop inhibitor antibodies following exposure to plasma. Haemostasis during surgery is achievable in such patients by recombinant activated factor VII (rFVIIa) at doses used in haemophilia A patients with an inhibitor to FVIII. However, thrombosis has occurred in three of 12 such patients.

Lower doses of rFVIIa therapy are safe and effective for surgical interventions in patients with severe FXI deficiency and inhibitors.

Severe FXI deficiency is a rare injury-related bleeding disorder. In patients with FXI inhibitors, surgeries may be treated using recombinant activated factor VII; however, treatment safety is a major concern and the best dosing regimen as well as mode of administration is still to be defined. We describe four patients with severe factor XI deficiency and inhibitors to FXI, undergoing eight (four major) surgical procedures treated with continuous infusion of rFVIIa.

Activated platelets mediate Staphylococcus aureus deposition on subendothelial extracellular matrix: the role of glycoprotein Ib.

Extracellular matrix (ECM) derived from bovine corneal endothelial cells was used as a model to study the role of platelets in Staphylococcus aureus interaction with the vascular subendothelium. In whole blood, S. aureus activated platelets, as demonstrated by P-selectin expression on the platelet membrane.

Increased platelet deposition on extracellular matrix under flow conditions in patients with antiphospholipid syndrome who experience thrombotic events.

Objective: To assess platelet function under defined flow conditions in patients with antiphospholipid syndrome (APS) and to correlate the results with thrombotic complications and the presence of subsets of antiphospholipid antibodies (aPL), lupus anticoagulant (LAC), and/or anticardiolipin antibodies (aCL).

Methods: We studied 88 randomized APS patients with or without a history of thrombosis. Seventeen patients with other thrombosis (no APS) and 26 healthy subjects served as controls.

Plasma replacement therapy during labor is not mandatory for women with severe factor XI deficiency.

Severe factor XI deficiency is an injury-related bleeding disorder. The risk of excessive post-partum hemorrhage in affected women has so far been evaluated in a relatively small number of patients and it is uncertain whether prophylactic treatment with fresh frozen plasma or factor XI concentrate is needed during or after vaginal or cesarean delivery. We retrospectively analyzed bleeding manifestations related to vaginal and/or cesarean deliveries in a cohort of 62 women with factor XI activity < 17 U/dl and evaluated whether replacement therapy is essential.

Inherited factor XI deficiency confers no protection against acute myocardial infarction.

Background And Purpose: Factor XI (FXI) contributes to thrombin generation thereby affecting fibrin formation and to down regulation of fibrinolysis by activation of thrombin-activatable fibrinolysis inhibitor (TAFI). The purpose of this study was to evaluate whether patients with severe FXI deficiency are protected against acute myocardial infarction (AMI).

Methods: The incidence of AMI in patients with severe FXI deficiency (FXI activity less than 15 U dL(-1)) whose age was 35 years or more was compared to the incidence of AMI in age and gender matched persons of the general population.

Diagnosis of thrombotic thrombocytopenic purpura based on modulation by patient plasma of normal platelet adhesion under flow condition.

We have designed a simple test for the early diagnosis and treatment monitoring of thrombotic thrombocytopenic purpura (TTP). We examined plasma from 24 TTP patients and normal plasma using a cone and plate(let) analyser (CPA). Test plasma was mixed with citrated normal whole blood (group O) and subjected to flow at a shear rate of 1800/s.