phosphorus-radioisotopes and Thrombosis

Since 1903 when polycythemia vera was designated by Osler as a new identity the clinical manifestations at the time of diagnosis--symptomatology, physical and hematological findings have become well known. Criteria for diagnosis have been established as well as treatment goals. However, agreement on how best to treat this disease has eluded the hematologists particularly as our understanding of the evolution of the hematological findings has become better known. The hemorrhagic and thrombotic complications and acute leukemia in patients managed with myelosuppressive regimens have come to the forefront. Criteria to be used in the comparison of treatment regimens are suggested from which in this author's opinion the use of 32P becomes the treatment of choice, but not all will agree.

Topics: Antineoplastic Agents; Hemorrhagic Disorders; Humans; Leukemia; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Remission Induction; Thrombosis

Topics: Anemia; Apoptosis; Clone Cells; Disease Progression; Erythropoiesis; Erythropoietin; Female; Growth Substances; Hematologic Tests; Hematopoietic Stem Cells; Humans; Iron; Leukemia, Myeloid; Male; Myeloproliferative Disorders; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Pregnancy; Pregnancy Complications, Hematologic; Receptors, Erythropoietin; Receptors, Growth Factor; Thrombocytosis; Thrombosis

The clinical course in both polycythaemia vera (PV) and essential thrombocythaemia (ET) is characterized by significant thrombohaemorrhagic complications and variable risk of disease transformation into myeloid metaplasia with myelofibrosis or acute myeloid leukaemia. Randomized studies have shown that the risk of thrombosis was significantly reduced in ET with the use of hydroxyurea (HU) and in PV with the use of chlorambucil or 32P. However, the use of chlorambucil or 32P has been associated with an increased risk of leukaemic transformation. Subsequently, other studies have suggested that both HU and pipobroman may be less leukaemogenic and as effective as chlorambucil and 32P for preventing thrombosis in PV. However, the results from these prospective studies have raised concern that even HU and pipobroman may be associated with excess leukaemic events in both ET and PV. The recent introduction of anagrelide as a specific platelet-lowering agent, the demonstration of treatment efficacy with interferon-alpha, and the revived interest in using low-dose acetylsalicylic acid provide the opportunity to initiate prospective randomized studies incorporating these treatments.

Topics: Adult; Aged; Aspirin; Chlorambucil; Disease Progression; Female; Hemorrhage; Humans; Hydroxyurea; Interferon-alpha; Leukemia, Myeloid; Leukemia, Radiation-Induced; Male; Middle Aged; Phlebotomy; Phosphorus Radioisotopes; Pipobroman; Polycythemia Vera; Primary Myelofibrosis; Prospective Studies; Quinazolines; Thrombocythemia, Essential; Thrombosis

Topics: Adult; Antineoplastic Agents; Busulfan; Follow-Up Studies; Hemorrhage; Humans; Hydroxyurea; Immunologic Factors; Interferon-alpha; Leukemia; Middle Aged; Phosphorus Radioisotopes; Plateletpheresis; Polycythemia Vera; Risk Factors; Thrombocythemia, Essential; Thrombosis

The PVSG was organized in 1967 to establish effective diagnostic criteria for polycythemia vera, to study the natural history of the disease and to define the optimal treatment. Although polycythemia vera and the other myeloproliferative diseases are relatively uncommon, the PVSG was able to accumulate well over 1,000 patients with these various disorders and to study them according to a total of 15 different protocols. PVSG-01, a long-term randomized controlled study of phlebotomy alone compared with the myelosuppressive agents, 32P or chlorambucil supplemented by phlebotomy, continues to receive follow-up data on 93% of surviving patients 18 years after initiation of the study. During its lifetime, PVSG has developed a widely accepted and highly effective set of criteria for the specific diagnosis of polycythemia vera as well as useful criteria for the diagnosis of essential thrombocythemia. It has gathered an enormous volume of data on the natural history of the myeloproliferative diseases and in particular on the nature of the prevalent complications, such as thrombotic events and hematologic and nonhematologic malignancies. With respect to the final question, the optimal treatment for polycythemia vera, it is apparent that the expectation of a single optimal therapy that would apply to all patients at all ages and stages of the disease was naive. Nevertheless considerable progress has been made. Moreover, the group has defined more precisely than ever before the nature of the complications of the disease and the association of the risks of specific complications with specific forms of therapy. It thus has made it possible to pose the next series of therapeutic questions that must be addressed in this disorder with a greater degree of sophistication than was previously possible.

Topics: Acute Disease; Age Factors; Bloodletting; Chlorambucil; Combined Modality Therapy; False Positive Reactions; Follow-Up Studies; Gastrointestinal Neoplasms; Gout; Hematocrit; Humans; Hydroxyurea; Leukemia; Phosphorus Radioisotopes; Platelet Aggregation; Platelet Count; Polycythemia Vera; Prospective Studies; Pruritus; Skin Neoplasms; Thrombosis

We hypothesized that restenosis after coronary stenting is predicted by elevated levels of markers of thrombus formation and inflammation. Plasma levels of representative markers of inflammation, the thrombin and plasmin activation systems and adhesion molecules were measured in 59 patients with stable angina pectoris before, immediately after and 6 hours (h), 12 h, 24 h, one month and six months after elective stent implantation (radioactive phosphorus-32 stents/RSs/ n = 16, bare-metal stents/BMSs/ n = 43). All patients underwent clinical and angiographic follow-up (FUP) six months after stenting. RSs had significantly higher angiographic severity of restenosis than BMSs (47.1 +/- 20.1% vs. 27.6 +/- 22.0%, p = 0.003). Repeated measures ANOVA revealed significant differences between the BMS and RS groups as regards the increases in plasma levels of vascular cell adhesion molecule-1 (VCAM-1, p = 0.022), plasminogen activator inhibitor-1 (PAI-1, p = 0.047), tissue-type plasminogen activator (tPA, p = 0.047) and CD40 ligand (CD40L, p = 0.038). tPA levels tended to increase immediately after stenting in both groups, whereas the PAI-1 level one month after stenting was elevated significantly only in the RS group. In the RS group, the plasma levels of CD40L were increased at 24 h and six months after stenting, and the VCAM-1 level rose immediately after stenting and remained high during the FUP. Multivariate analysis on pooled laboratory data of both groups revealed elevated levels of VCAM-1 at 12 h and at six months as significant predictors of the severity of stent restenosis. In conclusion, the process of inflammation and thrombosis occurring after coronary interventions seems to be prolonged and enhanced in patients with high-grade restenosis at the follow up.

Topics: Aged; CD40 Ligand; Chemokines; Chemokines, CXC; Coronary Restenosis; Coronary Stenosis; Female; Humans; Inflammation Mediators; Male; Middle Aged; Phosphorus Radioisotopes; Plasminogen Activator Inhibitor 1; Prognosis; Prospective Studies; Stents; Thrombosis; Time Factors; Tissue Plasminogen Activator

A significant proportion of patients with Essential Thrombocythaemia (ET) have thrombotic complications which have an important impact upon the quality, and duration of their life. We performed a retrospective cross sectional study of the prevalence of antiphospholipid antibodies (APA) in 68 ET patients. Compared to 200 "elderly" controls (>50 years) there was a significant increase in anticardiolipin IgM (p < 0.0001) and anti beta2 glycoprotein I (anti-beta2GPI) IgM (p < 0.0001) antibodies in ET. Thrombosis occurred in 10/20 with APA and 12/48 without, p = 0.04, relative risk 2.0 (95% confidence intervals 1.03-3.86): these patients did not differ in terms of other clinical features. The prevalence of thrombosis in patients with dual APA (6/7) was significant when compared to those with single APA (p = 0.02) and the remaining patients (p < 0.0002). Also anti-beta2GP1 IgM antibodies either alone, or in combination with another APA, were associated with thrombosis (p = 0.02). These results suggest that the prevalence of APA in ET and their influence upon thrombotic risk merit investigation in a larger study.

Topics: Adult; Aged; Aged, 80 and over; Alkylating Agents; Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Antibody Specificity; Antiphospholipid Syndrome; Autoantigens; Autoimmune Diseases; beta 2-Glycoprotein I; beta 2-Microglobulin; Child; Clone Cells; Cross-Sectional Studies; Female; Glycoproteins; Humans; Immunoglobulin G; Immunoglobulin M; Interferon-alpha; Male; Middle Aged; Phosphorus Radioisotopes; Platelet Aggregation Inhibitors; Prevalence; Retrospective Studies; Thrombocythemia, Essential; Thrombophilia; Thrombosis

Topics: Angioplasty, Balloon, Coronary; Animals; Coronary Artery Disease; Coronary Vessels; Equipment Design; Heparin; Humans; Phosphorus Radioisotopes; Rabbits; Recurrence; Stents; Swine; Technology Assessment, Biomedical; Thrombosis

Twenty-four arteries of rabbit ears, divided into two groups of 12 vessels each, were prepared and 32P-labelled platelets were infused. Arteriotomy/intimectomy was performed after 1 hr and in vivo platelet accumulation recorded for 2 hr. Group A comprised untreated control animals and group B was treated with 1 g hydroxyethyl starch (HES), MW 450,000 in 17 ml saline/kg b.w. (Plasma-steril). Vessel bleeding-times were normal, patency was improved, and intraluminal thrombotic material was reduced after HES treatment. Initial in vivo platelet accumulation was rapid and reached similar levels in both groups. However, the platelet accumulation curves decreased more frequently following HES than in the control group. HES does not prevent platelet accumulation at trauma sites, but reduces the sizes of the thrombi formed and may enhance disaggregation/fibrinolysis.

Topics: Animals; Arteries; Blood Coagulation; Blood Platelets; Dextrans; Ear, External; Female; Hydroxyethyl Starch Derivatives; Male; Microsurgery; Phosphorus Radioisotopes; Platelet Aggregation; Platelet Aggregation Inhibitors; Rabbits; Sodium Chloride; Thrombosis; Vascular Patency

Topics: Aspirin; Dipyridamole; Female; Hemorrhage; Humans; Male; Phosphorus Radioisotopes; Platelet Aggregation; Platelet Count; Polycythemia Vera; Thrombosis

The effect of bonding of heparin, via a glutaraldehyde-stabilized ionic complex, on the early thrombogenicity of polyurethane (PU) and expanded polytetrafluoroethylene (PTFE) (Gore-tex) as well as covalent bonding of heparin on PTFE was studied in vivo. Grafts 6 cm long and 4 mm in diameter were placed in the carotid arteries of sheep and perfused for 4 hours at 25 ml/min in order to accelerate thrombus formation. The thrombogenicity was determined by calculation of the percent of the luminal surface free of thrombus and patency. In addition, 32P-labelled platelet accumulation was determined in some of the grafts. The stabilized ionic bonding of heparin significantly reduced the early thrombogenicity of PU but had little effect on PTFE grafts; but the thrombogenicity of the latter was markedly decreased following covalent bonding of heparin. A regional distribution of platelet accumulation was found with the distal anastomoses showing the highest platelet deposition. By choice of an appropriate method of heparinization, a significant reduction of the thrombogenicity of PU and PTFE grafts was achieved.

Topics: Animals; Blood Vessel Prosthesis; Carotid Arteries; Carotid Artery Thrombosis; Female; Heparin; Isotope Labeling; Male; Phosphorus Radioisotopes; Platelet Count; Polytetrafluoroethylene; Polyurethanes; Sheep; Thrombosis

Microvascular anastomoses were performed under standardized conditions on the central artery of the ear in 8 rabbits. In all, 6 end-to-end and 5 end-in-end anastomoses were carried out. In 3 rabbits, one type of anastomosis was performed on each ear thus permitting simultaneous comparison of both types. Other than the local application of lidocaine, no anticoagulants or vasodilating agents were used. 32P labelled platelets were injected intravenously 2 hours before microvascular anastomoses were performed. All end-to-end anastomoses showed a rapid increase in radioactivity immediately after removal of the vessel clamps. The activity reached a peak some 300-600% above the initial value after approximately 30 minutes and then decreased. The patent vessels in the end-in-end group showed no increase in platelet activity and the difference between the two groups was significant during the first two hours. The results are interpreted as showing that platelet accumulation in patent vessels is more pronounced in end-to-end than in end-in-end anastomoses.

Topics: Animals; Arteries; Blood Platelets; Ear; Methods; Microsurgery; Phosphorus Radioisotopes; Rabbits; Thrombosis

Three hundred and three cases of polycythaemia vera were treated between 1949 and 1961 using radioactive phosphorus, the minimum follow-up for the patients in the group being 12 years and the maximum 24 years. Two hundred and thirty three patients died, the median duration of survival after the first treatment with phosphorus being 10 years (i.e. 12 years after the diagnosis was made). 59 patients died of the vascular complications of polycythaemia, 76 of leukaemia or myelofibrosis. The total number of deaths due to vascular complications up to the tenth year exceeded the total number of deaths due to haematological complications (leukaemia or myeloid metaplasia). At the end of the 11th year the opposite was true. From the ninth year onwards, acute leukaemia and myelofibrosis represent more than 40 p.cent of deaths of known cause and the annual probability of death from a haematological cause for the surviving patients increases regularly until the fifteenth year when it reaches approximately 5 p.cent of the patients at risk. However the median survival of patients dying from acute leukaemia or myeloid splenomegaly is slightly longer than that of patients dying from other causes, this confirming that these disorders would appear to represent the terminal phase in the course of polycythaemia vera.

Topics: Acute Disease; Aged; Female; Follow-Up Studies; Hemorrhage; Humans; Kidney Neoplasms; Leukemia; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Splenomegaly; Thrombosis

Topics: Busulfan; Chronic Disease; Diagnosis, Differential; Hemorrhage; Humans; Phosphorus Radioisotopes; Polycythemia Vera; Thrombosis

Topics: Aged; Blood Platelets; Blood Transfusion, Autologous; Bloodletting; Busulfan; Erythrocyte Count; Female; Hematocrit; Hemorrhage; Humans; Male; Middle Aged; Peptic Ulcer; Phosphorus Radioisotopes; Polycythemia Vera; Postoperative Complications; Surgical Procedures, Operative; Thrombosis

Topics: Analysis of Variance; Animals; Aorta; Aortic Diseases; Arteriosclerosis; Autoanalysis; Blood Platelets; Carbon Radioisotopes; Catheterization; Cholesterol; Chromatography, Gas; Linoleic Acids; Lipid Metabolism; Oleic Acids; Phospholipids; Phosphorus Radioisotopes; Rabbits; Thrombosis

Topics: Animals; Dextrans; Hemostatics; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Porifera; Radioactivity; Rats; Reserpine; Thrombosis