fibrinopeptide-a and Thrombocytopenia

1. The lack of a general agreement on the definition of PE makes the interpretation of laboratory findings in different series of these patients difficult. 2. Thrombocytopenia is the most common hemostatic abnormality in patients with PE and is caused by platelet consumption. 3. There is little concrete evidence that thrombin mediates the thrombocytopenia in most of these patients. 4. Immune mechanisms or severe vasospasm with resultant endothelial damage may contribute to the thrombocytopenia in some patients.

Topics: Anemia, Hemolytic; Disseminated Intravascular Coagulation; Eclampsia; Epoprostenol; Factor VIII; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Hypertension; Platelet Count; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Thrombin; Thrombocytopenia; Thromboxane A2

Almost a third of patients who undergo peripheral bypass procedures do not have suitable veins, making the use of prosthetic materials necessary. Prosthetic materials can cause platelet adhesion and activation of the coagulation cascade on the graft. One potential strategy to reduce this thrombogenicity is to covalently bind heparin to the endoluminal surface of grafts. This human in vivo study examined systemic effects of the endoluminal heparin and addressed whether graft implantation results in (1) a measurable reduction of systemic markers of hemostasis activation compared with control grafts and (2) antibody formation against heparin, potentially responsible for heparin-induced thrombocytopenia (HIT).. The study included 20 patients undergoing femoropopliteal bypass grafting, of whom 10 received a standard Gore-Tex Thin Walled Stretch Vascular Graft (W. L. Gore & Associates, Flagstaff, Ariz) and 10 received a heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft (Gore-Tex Propaten Vascular Graft). Blood samples were drawn before and directly after the operation and at days 1, 3, 5, and week 6 after surgery. Established markers of in vivo activation of platelets and blood coagulation (prothrombin fragment 1+2, fibrinopeptide A, soluble glycoprotein V, thrombin-antithrombin complexes, and D-dimers) were measured using standard commercially available techniques. Antiplatelet factor 4/heparin antibody titers were measured using a commercially available enzyme-linked immunosorbent assay, and platelet counts were determined.. No statistical differences were observed in any of the markers of in vivo activation of platelets and blood coagulation between patients receiving Propaten or control ePTFE. Moreover, no antibodies against heparin could be demonstrated up to 6 weeks after implantation.. No measurable effect of heparin immobilization on systemic markers of hemostasis was found using a heparin-bonded ePTFE graft in vivo. Also, no antibodies against heparin could be detected up to 6 weeks after implantation.

Topics: Aged; Antibodies; Anticoagulants; Antithrombin III; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Hemostasis; Heparin; Humans; Male; Middle Aged; Peptide Fragments; Peptide Hydrolases; Peripheral Vascular Diseases; Platelet Count; Platelet Glycoprotein GPIb-IX Complex; Polytetrafluoroethylene; Prosthesis Design; Prothrombin; Thrombocytopenia; Thrombosis; Time Factors; Treatment Outcome; Vascular Patency

Hemodialysis induces thrombocytopenia and activation of coagulation. The severity of this reaction depends on the kind of membrane. In this study, we present the results of determination of platelet count, and of different factors of coagulation in 10 stable dialysis patients. Measurements were performed at the start and after 15 and 45 min of dialysis. Samples were taken before and after the dialyzer. All 10 patients were treated consecutively and in a random order during 14 days with the following membranes: polyacrylonitrile (Filtral 12, Hospal), hemophan (GFS 120 Plus, Gambro, and Bio-Nephros HF Andante, Organon), polysulfone (F6, Fresenius), cuprammonium (AM50-BIO, Asahi) and cellulose acetate (Duo-Flux, Cordis-Dow). The cellulose acetate membrane induced a small but significant drop of mean platelet count [results are mean (SEM)]: from 245,000 (17,000) to 224,000 (16,000)/microliters after 15 min. With the same membrane a dramatic increase after 15 min was noted of 6-keto-PGF1 alpha from 56.3 (9) to 146.7 (35.7) pg/ml. The other membranes did not influence significantly prostanoid levels and platelet count. During dialysis no significant changes of fibrinopeptide A (FPA) and von Willebrand factor (VWF) were observed. Nevertheless, predialysis FPA and beta-thromboglobulin (beta TG) concentrations were lowest after 14 days of treatment with cellulose acetate and polyacrylonitrile membranes. It is concluded that the activation of coagulation depends on the membrane used. The activation may be dominated by one single system (e.g. prostanoids). The different predialysis concentration of some of the factors suggests interference of the dialysis membrane with the activation of coagulation during the interdialytic period.

Topics: 6-Ketoprostaglandin F1 alpha; Antigens; Blood Coagulation; Cellulose; Fibrinopeptide A; Hemostasis; Humans; Kidneys, Artificial; Membranes, Artificial; Platelet Activation; Platelet Count; Renal Dialysis; Thrombocytopenia; von Willebrand Factor

For 11 patients with confirmed heparin-induced thrombocytopenia, we used reversible platelet inhibition with iloprost, a stable prostacyclin analogue, to permit safe heparin administration for cardiac (n = 9) or vascular (n = 2) operations. In vitro, iloprost (0.01 mumol/L) prevented both heparin-induced platelet aggregation and 14C-serotonin release in all patients. Therefore, intraoperatively, a continuous infusion of iloprost was started before administration of heparin and was continued until 15 minutes after administration of protamine. For cardiac patients, after heparin administration, the whole blood platelet count did not change (171,000 +/- 29,000/microL versus 174,000 +/- 29,000/microL, mean +/- standard error of the mean); no spontaneous platelet aggregation was observed, and plasma levels of the alpha-granule constituents platelet factor 4 and beta-thromboglobulin increased from 38 +/- 14 and 140 +/- 18 ng/mL to 591 +/- 135 and 235 +/- 48 ng/mL, respectively. Fibrinopeptide A levels actually decreased from 287 +/- 150 to 27 +/- 6 ng/mL. Furthermore, adenosine diphosphate-induced platelet activation was preserved, postoperative bleeding times were unchanged, and no heparin-related deaths occurred. Similar results were obtained in both vascular patients. We conclude that temporary platelet inhibition with iloprost now permits safe heparin administration in all patients with heparin-induced thrombocytopenia who require a cardiac or vascular operation.

Topics: Adult; Aged; Aspirin; beta-Thromboglobulin; Bleeding Time; Epoprostenol; Fibrinopeptide A; Heparin; Humans; Iloprost; Intraoperative Period; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Platelet Factor 4; Thrombocytopenia; Thromboxane B2

Recurrent thrombocytopenia, thrombosis, or sudden death may develop in patients with heparin-induced thrombocytopenia who are reexposed to heparin. Three patients came to us in whom a diagnosis of heparin-induced thrombocytopenia had been made on the basis of clinical and serologic evidence; these patients required reexposure to heparin because of urgent cardiac surgery. Therefore, we evaluated the ability of iloprost (ZK36374), a new analogue of prostacyclin, to prevent heparin-dependent activation of platelets and thereby permit obligatory heparinization for safe extracorporeal circulation. Before operation, we demonstrated that iloprost prevented both heparin-dependent platelet aggregation and tritiated (3H)-serotonin release in vitro. Therefore a continuous infusion of iloprost was begun 1 hour before heparinization and was continued throughout cardiopulmonary bypass and for an additional 15 minutes after protamine administration. The mean platelet count of 130,000/microliters before operation remained stable, and no spontaneous platelet aggregation was observed in samples of platelet-rich plasma obtained before cardiopulmonary bypass but after heparin administration. Similarly, after heparin administration but before bypass, platelet responsiveness to adenosine diphosphate remained unchanged when compared with preoperative values. Plasma levels of platelet factor 4 increased from 26 +/- 1 ng/ml (mean +/- standard error) to 843 +/- 383 ng/ml after heparin administration but actually decreased throughout cardiopulmonary bypass to 52 +/- 25 ng/ml. Beta-thromboglobulin levels increased from 103 +/- 16 to 244 +/- 94 ng/ml with heparinization. The mean bleeding time was 10.5 minutes preoperatively and 13.3 minutes postoperatively. The mean amount of postoperative chest tube drainage (duration: 12 hours) was 432 +/- 67 ml. Thus, despite the confirmed presence of heparin-dependent platelet-activating factor in the plasma of these three patients, iloprost prevented heparin-induced platelet activation during cardiopulmonary bypass while preserving platelet function, as would be desired for postoperative hemostasis.

Topics: Adult; Cardiopulmonary Bypass; Cardiovascular Agents; Epoprostenol; Fibrinopeptide A; Heparin; Humans; Iloprost; Middle Aged; Platelet Aggregation; Platelet Count; Platelet Factor 4; Thrombocytopenia; Thromboxane B2

Topics: Aged; Antithrombins; Arginine; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Female; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Pipecolic Acids; Platelet Aggregation Inhibitors; Renal Dialysis; Sulfonamides; Thrombocytopenia; Thrombosis

Hemostatic and platelet function studies were performed prospectively on 61 preeclamptic patients and 24 healthy pregnant control patients to delineate possible causes of thrombocytopenia in preeclampsia. Thrombocytopenia occurred in 50% of the preeclamptic patients, and was accompanied by qualitative platelet defects as shown by an increased bleeding time and decreased biosynthesis of thromboxane A2. All patients had normal routine coagulation and protamine sulphate paracoagulation assays. All nulliparous patients had normal levels of fibrinopeptide A, but approximately 60% of parous patients had slight elevations of fibrinopeptide A. Elevated levels of platelet-associated immunoglobulin G (IgG) were demonstrated in 35% of all preeclamptic patients and were inversely correlated (r = -0.524) with the severity of the thrombocytopenia. This study indicates that, at least in nulliparous patients, thrombin action is not a major contributor to the development of thrombocytopenia in preeclampsia. The observation of elevated levels of platelet-associated IgG suggests that immune mechanisms could contribute to the thrombocytopenia in some patients.

Topics: Adult; Blood Coagulation Tests; Female; Fibrinopeptide A; Hemostasis; Humans; Immunoglobulin G; Platelet Count; Platelet Function Tests; Pre-Eclampsia; Pregnancy; Prospective Studies; Thrombocytopenia

Topics: Aged; Cholinesterases; Female; Fibrinopeptide A; Humans; Liver; Liver Cirrhosis; Male; Middle Aged; Platelet Count; Spleen; Thrombin; Thrombocytopenia

Plasma and serum assays of beta-thromboglobulin (BTG) and platelet factor 4 (PF4), and plasma fibrinopeptide A (FPA) were measured in adults with cyanotic congenital heart disease to characterize further the hemostatic disorder. Artifactual elevations of plasma BTG, PF4, and FPA appeared to occur occasionally when a 21 or 22 gauge needle was used to collect blood. The high packed red cell volume was probably the cause. Use of a larger caliber needle (20 gauge) appeared to lessen the problem. Normal plasma FPA levels (20 gauge needle) in 8 of 9 patients suggest that chronic intravascular coagulation is not common in these patients. Serum BTG and PF4, used to estimate total platelet content of these proteins, were normal to slightly increased. That levels were not reduced implies that platelets do not usually circulate in a "spent" state. Therapeutic phlebotomy in 8 patients was associated with small decreases in plasma BTG and PF4 of uncertain clinical significance. Five of 14 patients had elevated plasma BTG with normal to only minimally increased plasma PF4. However, 10 of 10 patients tested were found to have reduced creatinine clearance, and therefore the relative contributions of platelet secretion and reduced BTG catabolism in the kidney to elevated plasma BTG levels are unclear.

Topics: Adolescent; Adult; Animals; Beta-Globulins; beta-Thromboglobulin; Blood Coagulation Factors; Blood Platelet Disorders; Blood Specimen Collection; Fibrinogen; Fibrinopeptide A; Heart Defects, Congenital; Humans; Macaca mulatta; Middle Aged; Needles; Platelet Factor 4; Polycythemia; Radioimmunoassay; Rats; Thrombocytopenia

Topics: Antibodies; Aspirin; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Cell Adhesion; Cell Communication; Cyclooxygenase Inhibitors; Disseminated Intravascular Coagulation; Epoprostenol; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Indomethacin; Monocytes; Neoplasm Transplantation; Neoplasms; Syndrome; Thrombocytopenia; Thrombocytosis; Thromboembolism; Thromboplastin

Topics: Adult; Aged; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Female; Fibrinopeptide A; Humans; Liver Cirrhosis; Male; Middle Aged; Platelet Count; Thrombin; Thrombocytopenia

The mechanism of isolated thrombocytopenia in septicemia is unknown, but compensated disseminated intravascular coagulation (DIC) has been suggested as a possible cause. To investigate this possibility, platelet counts and sensitive assays for in vivo thrombin and plasmin generation, including fibrinogen gel chromatography and fibrinopeptide A (FPA) assays, were obtained on 31 septicemic patients. Fifteen of 17 patients with gram-negative septicemia and 8 of 14 patients with gram-positive septicemia had thrombocytopenia. Platelet survival studied demonstrated a decreased platelet survival. In 11 of 12 patients with severe thrombocytopenia (platelet count less than 50,000mul), there was laboratory evidence of intravascular coagulation. In contrast, there was little evidence of intravascular coagulation in 8 of 11 patients with moderate thrombocytopenia (platelet counts 50,000 to less than 150,000/mul) or in 7 of 8 patients with normal platelet counts. This report indicates that while DIC accompanies thrombocytopenia in many patients with severe thrombocytopenia, there is frequently little evidence for intravascular coagulation in patients with moderate thrombocytopenia. It is apparent that factors other than intravascular thrombin must play a role in producing the thrombocytopenia of septicemia.

Topics: Adult; Aged; Blood Platelets; Cell Survival; Disseminated Intravascular Coagulation; Female; Fibrinogen; Fibrinolysin; Fibrinopeptide A; Humans; Male; Middle Aged; Platelet Count; Sepsis; Thrombin; Thrombocytopenia