Marcos Pino

Increased local procoagulant action: a mechanism contributing to the favorable hemostatic effect of recombinant FVIIa in PLT disorders

BACKGROUND: Recombinant FVIIa (rFVIIa) has been shown to improve hemostasis in patients with thrombocytopenia and to prevent or control bleeding episodes in patients with inherited deficiencies of major PLT glycoproteins, but the mechanism of action is not well understood.

Infusible platelet membranes improve hemostasis in thrombocytopenic blood: experimental studies under flow conditions.

BACKGROUND : The potential hemostatic effect of infusible platelet membranes (IPM; Cyplex, Cypress Bioscience) prepared from outdated human platelets is investigated.

Hemostatic effect of activated recombinant factor VII (rFVIIa) in liver disease: studies in an in vitro model

BACKGROUND/AIMS There is clinical evidence for the efficacy of activated recombinant factor VII (rFVIIa) in patients with cirrhosis. The exact mechanism of action of rFVIIa in this clinical condition is unknown. We have explored effects of rFVIIa on hemostasis in cirrhotic patients using an in vitro perfusion technique. METHODS Blood samples were drawn from control donors or from 11 patients previously diagnosed with cirrhosis (seven Child-Pugh B and four Child-Pugh C) and anticoagulated with low molecular weight heparin. rFVIIa was added to blood samples at therapeutic concentrations (0.5 or 1 microg/ml of plasma) and blood was recirculated through annular chambers containing damaged vascular segments. Presence of platelets and fibrin on the subendothelium were morphometrically quantified. RESULTS Cirrhotic patients showed a diminished platelet interaction with the subendothelium compared to healthy donors (17.3% (9.28-28.88%) vs. 26.16% (19.96-54.5%), P<0.05). After addition of rFVIIa to cirrhotic samples, no differences in platelet covered surface were observed. However, fibrin formation was significantly improved after the addition of rFVIIa (from 51.81% (3.02-86.68%) to 86.94% (30.03-93.18%) and 89.05% (45.65-93.84%), respectively, P<0.05). CONCLUSIONS Our data confirm a defective interaction of platelets with the subendothelium in cirrhotic patients. rFVIIa improved local fibrin formation at damaged sites and this mechanism could explain the beneficial action of rFVIIa in cirrhotic patients.

Impact of experimental haemodilution on platelet function, thrombin generation and clot firmness: effects of different coagulation factor concentrates

BACKGROUND Haemodilution during resuscitation after massive haemorrhage may worsen the coagulopathy and perpetuate bleeding. MATERIALS AND METHODS Blood samples from healthy donors were diluted (30 and-60%) using crystalloids (saline, Ringers lactate, Plasmalyte(TM)) or colloids (6% hydroxyethylstarch [HES130/0.4], 5% human albumin, and gelatin). The effects of haemodilution on platelet adhesion (Impact R), thrombin generation (TG), and thromboelastometry (TEM) parameters were analysed as were the effects of fibrinogen, prothrombin complex concentrates (PCC), activated recombinant factor VII (FVIIa), and cryoprecipates on haemodilution. RESULTS Platelet interactions was already significantly reduced at 30% haemodilution. Platelet reactivity was not improved by addition of any of the concentrates tested. A decrease in TG and marked alterations of TEM parameters were noted at 60% haemodilution. HES130/0.4 was the expander with the most deleterious action. TG was significantly enhanced by PCC whereas rFVIIa only caused a mild acceleration of TG initiation. Fibrinogen restored the alterations of TEM parameters caused by haemodilution including those caused by HES 130/0.4. Cryoprecipitates significantly improved the alterations caused by haemodilution on TG and TEM parameters; the effects on TG disappeared after ultracentrifugation of the cryoprecipitates. DISCUSSION The haemostatic alterations caused by haemodilution are multifactorial and affect both blood cells and coagulation. In our in vitro approach, HES 130/0.4 had the most deleterious effect on haemostasis parameters. Coagulation factor concentrates did not improve platelet interactions in the Impact R, but did have favourable effects on coagulation parameters measured by TG and TEM. Fibrinogen notably improved TEM parameters without increasing thrombin generation, suggesting that this concentrate may help to preserve blood clotting abilities during haemodilution without enhancing the prothrombotic risk.

Evaluation of effects of rofecoxib on platelet function in an in vitro model of thrombosis with circulating human blood.

Background  Cyclooxygenase (COX)‐2‐selective non‐steroidal anti‐inflammatory drugs have been used for anti‐inflammatory therapy. However, it has also been described that they may increase risk of cardiovascular events.

Hemostatic effect of activated recombinant factor VIIa in Bernard‐Soulier syndrome: studies in an in vitro model

To the Editor: Bernard-Soulier syndrome (BSS) is a rare disorder associated with the lack or dysfunction of the platelet (PLT) glycoprotein complex Ib-V-IX. These PLTs have impaired interaction with the subendothelium and affected persons experience repeated mucosal bleeding. Transfusion of PLT concentrates may be required to control severe bleeding. Unfortunately, some patients develop antibodies and refractoriness to further PLT transfusions. Recombinant factor VIIa (rFVIIa) is indicated for treating bleeding episodes in patients with hemophilia A or B with inhibitors. A recent study from our group found that rFVIIa facilitates fibrin formation on damaged vasculature using blood from patients with hemophilia and inhibitors. 1 Clinical experience suggests that rFVIIa may have a potential role in the treatment of bleeding in patients with quantitative and qualitative PLT disorders. 2

Platelets interact with tissue factor immobilized on surfaces: effects of shear rate

Background  While procoagulant activities of Tissue Factor (TF) have been widely investigated, its possible pro‐adhesive properties towards platelets have not been studied in detail.

Antithrombotic effect of a new nitric oxide donor (LA419) on experimental thrombogenesis

Background  The ability of nitrous compounds to donate nitric oxide (NO), an agent with vasodilating and inhibitory effects on platelet function, has been considered a useful pharmacologic strategy for cardiovascular complications. The purpose of this study was to investigate the effects of a new NO donor, LA419, on platelet interaction in an ex vivo model with human blood circulating through collagen‐rich surfaces.

Concentrates containing factor IX could improve haemostasis under conditions of thrombocytopenia: studies in an in vitro model

Background and Objectives We explored the effect on haemostasis of different factor IX (FIX) concentrates under thrombocytopenic conditions using an in vitro perfusion technique.