Showing papers on "Blood Platelet Disorders published in 2008"

Platelet prothrombin converting activity in hereditary disorders of platelet function.

Abstract: Prothrombinase activities of platelets have been measured in diluted platelet-rich plasma using a chromogenic substrate assay and purified coagulation factors No abnormalities in prothrombinase activities were found for platelets from patients with storage pool disease (dense-body deficiency), grey platelet syndrome, and Glanzmann's thrombasthenia It is concluded that neither release of dense bodies and alpha-granules nor aggregation of platelets are essential prerequisites for exposure of a procoagulant surface Platelets from patients with Bernard-Soulier syndrome, however, have approximately 10-fold higher prothrombinase activities in the non-stimulated form than normal non-stimulated platelets The increased procoagulant activity cannot be completely ascribed to an increase in platelet size It is suggested that the increased prothrombinase activity reflects an increased exposure of phosphatidylserine at the outer surface of non-stimulated Bernard-Soulier platelets, earlier described by Perret et al (1983)

Quebec platelet disorder: features, pathogenesis and treatment.

Abstract: Quebec platelet disorder (QPD) is a rare, autosomal-dominant, inherited bleeding disorder that is associated with unique abnormalities in fibrinolysis. Its hallmark features are delayed-onset bleeding following hemostatic challenges that responds to fibrinolytic inhibitor therapy and increased expression and storage of the fibrinolytic enzyme urokinase plasminogen activator in platelets, without increased plasma urokinase plasminogen activator or systemic fibrinolysis. The increased urokinase plasminogen activator in QPD platelets is only partially inhibited, and, as a result, there is intraplatelet generation of plasmin, and secondary degradation of many platelet alpha-granule proteins. During clot formation, the urokinase plasminogen activator released by QPD platelets leads to platelet-dependent increased fibrinolysis, and this is postulated to be a major contributor to QPD bleeding. The focus of the present review is to summarize the current state of knowledge on QPD, including the history of this disorder, its clinical and laboratory features, and recommended approaches for its diagnosis and treatment.

Prevalent platelet dysfunction in patients with aortic valve disease.

Abstract: BACKGROUND AND AIM OF THE STUDY: In patients with heart valve disease, the valve leaflets display a gapped, rough endothelial lining often covered with calcified areas. As a consequence, blood flow is disturbed and a stimulation of components of the hemostasis system is assumed. The possible mechanisms of this process are, however, unclear at present. METHODS: Platelet function was studied in 660 patients considered for isolated coronary artery bypass graft (CABG) surgery, and in 421 patients considered for single aortic valve replacement (AVR). Platelet function was monitored preoperatively using the platelet function analyzer device (PFA-100). The test results were reported as closure time of the membrane hole at the end of a capillary tube. The von Willebrand factor antigen, and its collagen-binding activity, were also determined among subgroups of 40 AVR and 50 CABG candidates. RESULTS: Platelet dysfunction was displayed by only 22% of CAD patients, but by 83% of AVR candidates. The mean PFA closure time in AVR patients was considerably higher than in CAD patients (231 +/- 59 s versus 153 +/- 60 s, respectively; p < 0.01). The mean platelet volume, platelet distribution width and von Willebrand factor collagen binding and antigen levels did not differ between the patient groups. CONCLUSION: It is assumed that, due to disturbed flow and shear exposition, following an initial activation, the platelets are partially degranulated, shed microparticles, and might become involved in the pathogenesis of microvascular dysfunction and thrombotic events in patients with aortic valve disease.

Characteristics, diagnosis, and treatment of inherited platelet disorders in mammals.

Abstract: Inherited intrinsic platelet disorders have been identified in dogs, cattle, horses, and cats as well as other animals. The prevalence of mutations in some breeds is high, making these disorders potentially as common as von Willebrand disease in certain breed lineages.

The use of recombinant activated factor VII in platelet-associated bleeding

Abstract: Recombinant activated factor VII (rFVIIa) was originally developed for the treatment of spontaneous and surgical bleeding of hemophiliacs with inhibitors. Along with the elucidation of its molecular mechanism of action, rFVIIa has been successfully used over the last few years in a wide range of non-hemophilic bleeding conditions. The aim of this review is to summarize the current clinical experience on the use of rFVIIa in the management of bleeding associated with congenital or acquired platelet disorders.

Use of recombinant factor VIIa for hip replacement surgery in a patient with severe factor XI deficiency and drug‐induced platelet defect

Abstract: Patients with factor XI (FXI) deficiency rarely develop spontaneous bleeding, As shown in several case reports by Rosenthal et al. [1,2], bleeding usually occurs following trauma or surgery. Similar observations were made by Ragni et al. [3] in 25 FXIdeficient kindreds. No patient experienced deep muscle haematoma, haemarthroses, or bleeding into central nervous system (CNS), gastrointestinal tract, or retroperitoneal space. Bleeding is especially severe at sites with high fibrinolytic activity [4]. If specific FXI concentrates are not available, recombinant factor VIIa [FVIIa; eptacog alfa (activated)] is a treatment option, especially, in cases where fluid overload induced by fresh frozen plasma (FFP) should be avoided. We report the case of an 85year-old female with hip fracture who underwent hip replacement surgery and was treated perioperatively with eptacog alfa (activated) in combination with tranexamic acid. The patient was admitted for surgery of an acute traumatic hip fracture. Several years before, FXI deficiency had been diagnosed after severe postoperative bleeding that followed cholecystectomy, requiring massive transfusion. The patient reported frequent haematomas and increased bleeding after minor injury since childhood, and occasional nosebleeds. Coagulation and clinical chemistry analyses were done using reagents and instrumentation from DadeBehring, Marburg, Germany. Laboratory diagnostics showed a FXI level below the detection limit of 3%, with otherwise normal coagulation factors (Table 1). The activated partial thromboplastin time (aPTT) using Actin FS reagent was prolonged; prothrombin time was normal. Platelet aggregation tests showed moderately impaired epinephrin-induced aggregation, presumably owing to treatment with ibuprofen. Expression of GP IIb/IIIa and GP Ib/IX were normal in flow-cytometric analysis (FACS) using reagents and instrumentation from Becton Dickinson, Heidelberg, Germany. The patient received 1 g of tranexamic acid and 4.8 mg (80 lg kg body weight) of eptacog alfa (activated) before surgery, 2.4 mg (40 lg kg body weight) of eptacog alfa (activated) 4 h after the initial bolus, and 1.2 mg (20 lg kg body weight) after 8, 16, and 24 h, resulting in a total dose of 10.8 mg or 180 lg kg body weight. Additional doses of 1 g or tranexamicacidwereadministeredafter8,16, and24 h. Total hip replacement surgery was performed without complications. Total intraand postoperative blood loss was 600 mL, which is within the expected range for patients without coagulation disorders. The patient received a total of one unit of erythrocyte concentrate, and 100 mL of re-transfused cell saver blood. Initial haemoglobin level was 10.7 g dL, haematocrit was 31%. The lowest haemoglobin level was 7.3 g dL, lowest haematocrit was 21%, measured 4 h after the start of surgery. After transfusion, haemoglobin level was 10.2 g dL, haematocrit was 29%, and remained stable. A drop in platelet count and fibrinogen level is related to intraoperative blood loss. d-dimer levels were elevated before surgery as a consequence of trauma and haematoma, with a further increase during surgery, and declining levels after surgery. About 4 h after surgery, the patient complained of chest pain. An electrocardiogram (ECG) revealed no Correspondence: Prof. Dr Carl-Erik Dempfle, I.Department of Medicine, University Hospital of Mannheim, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany. Tel.: +49-621-383-4002; fax: +49-621-383-3820; e-mail: carl-erik.dempfle@med.ma.uni-heidelberg.de

Acquired platelet dysfunction with spontaneous intramuscular hematoma and compartment syndrome in cirrhosis.

Abstract: Cirrhosis patients are at high risk for bleeding as a result of decreased platelet counts and impaired function, defective production of coagulation factors and abnormalities in clot lysis. The authors report the case of a 58 year-old man with cryptogenic cirrhosis who presented initially with intramuscular hematoma in the thigh which progressed to compartment syndrome. The patient developed disseminated progressive intramuscular hematomas in the muscles of chest, abdomen and finally retroperitoneal hemorrhage secondary to probable accelerated intravascular coagulation and fibrinolysis (AICF) culminating in death. This case highlights many of the common coagulation abnormalities seen in cirrhosis. The authors speculate the sequence of events in our patient at every level of the coagulation cascade which could have lead to this fatal outcome.