phosphorus-radioisotopes and Hemorrhage

Hydroxyurea is an old drug that is often used to control essential thrombocythemia and polycythemia vera in patients with high-risk disease. It is usually well tolerated and cheap and has been proven effective in many studies for the prevention of thrombohemorrhagic complications associated with these disorders. However, many clinicians are reluctant to use it because of the perceived risk of progression to acute leukemia. Several recent, large studies have given this drug a new lease on life. Relevant results from these studies are discussed, and the risk of leukemia is placed in perspective to demonstrate that hydroxyurea remains the drug of choice in patients with either of these disorders.

Topics: Aged; Agranulocytosis; Alkylating Agents; Clinical Trials as Topic; Combined Modality Therapy; Disease Progression; Evidence-Based Medicine; Hemorrhage; Humans; Hydroxyurea; Leukemia, Myeloid, Acute; Middle Aged; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Thrombocythemia, Essential; Thrombophilia

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

This study was performed to prospectively evaluate the safety, efficacy, and cost of injecting P-colloid into joints of children with hemophilia and synovitis to decrease the rate of joint bleeding.. Eligibility included a diagnosis of hemophilia, history of more than six hemorrhages into a joint within a 6-month period, and evidence of synovitis by objective imaging. With written, informed consent, 0.25 to 1.0 mCi of P-colloid was injected into the problem joints. Safety was monitored by external beta-scanning and physical assessment. Efficacy was determined by analysis of the change in joint hemorrhage frequency from 6 months before and up to 96 months after the injection using a signed-rank test. Physical assessment and pain assessment were analyzed similarly using values obtained within 1 week before and 6 months after the radiosynoviorthesis. Cost was modeled using charges from the authors' institution in relation to existing alternative therapies.. One hundred injections were given into 91 joints in 59 children. Seven children had high-titer neutralizing antibodies to factor VIII or IX. Nine children were infected with HIV. Joints injected included 44 ankles, 19 knees, 27 elbows, and 1 shoulder. Nine joints required reinjection. All children showed a significant decrease in bleeding rate (P < 0.0001) and pain (P = 0.03), with improved physical function (P = 0.02). In one child acute lymphocytic leukemia developed, but it was judged unrelated to the two P injections that he had received 3 and 10 months before the leukemia diagnosis. There were no cases of bleeding, infection, or inflammation caused by the injection. Cost was substantially less than medical and surgical alternatives.. Radiosynoviorthesis is effective in limiting the frequency of joint hemorrhage, decreasing pain and improving function in children with hemophilia. However, long-term safety studies are needed.

Topics: Adolescent; Adult; Ankle; Child; Child, Preschool; Cost-Benefit Analysis; Elbow; Female; Hemophilia A; Hemorrhage; Humans; Injections; Knee; Magnetic Resonance Imaging; Male; Phosphorus Radioisotopes; Radionuclide Imaging; Synovitis; Time Factors; Treatment Outcome

The principal medical consequence of haemophilia is the development of arthropathy, initiated by a haemarthrosis giving rise to chronic synovitis. Traditional methods of synovectomy include open excision and arthroscopy each of which require substantial amounts of clotting factor concentrate for several weeks, and in the case of open synovectomy, is often associated with loss of range of motion and arthrofibrosis. Radiosynovectomy, the intra-articular injection of low penetration radiocolloids, has been utilized outside the United States for over 20 years. Since 1988, our centre has performed 170 radiosynovectomies utilizing 32P chromic phosphate (32P). This study reports results of 130 32P radiosyovectomies with an average follow-up of 36.5 months (6-140 months). For primary procedures, excellent and good results (haemarthrosis reduction from 75 to 100%) were obtained in 79.2% of cases at 6 months to 8 years. For repeat procedures a combination of excellent and good results were obtained in 62.4% of cases at 6 months to 3 years. Regression analysis showed no correlation between results and age or degree of arthropathy. Radiation was well contained within the joint. There were no observed or identified complications. The procedure is highly cost effective in comparison to open surgical or arthroscopic synovectomy.

Topics: Adolescent; Adult; Age Factors; Child; Child, Preschool; Chromium Compounds; Chronic Disease; Combined Modality Therapy; Follow-Up Studies; Hemarthrosis; Hemophilia A; Hemorrhage; Humans; Injections, Intra-Articular; Middle Aged; Phosphates; Phosphorus Radioisotopes; Retrospective Studies; Risk Assessment; Synovectomy; Synovitis; Treatment Outcome

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

Topics: Choroid Neoplasms; Female; Hemorrhage; Humans; Melanoma; Middle Aged; Phosphorus Radioisotopes

A malignant melanoma of the choroid presented with a massive vitreous hemorrhage which prevented any view of the posterior pole. The diagnosis was confirmed by the results of a radioactive phosphorus test and ultrasonography. In eyes with opaque media, these tests will ofter prevent delays in diagnosis.

Topics: Aged; Choroid; Choroid Neoplasms; Eye Diseases; Hemorrhage; Humans; Male; Melanoma; Phosphorus Radioisotopes; Radionuclide Imaging; Ultrasonography; Vitreous Body

Topics: Adolescent; Adult; Aged; Cataract; Evaluation Studies as Topic; Eye Diseases; Eye Neoplasms; Female; Hemorrhage; Humans; Male; Melanoma; Middle Aged; Panophthalmitis; Phosphorus Radioisotopes; Retinal Detachment; Time Factors; Ultrasonography; Uveal Diseases; Vitreous Body

The prevention of recurrences of bladder cancer was attemped in 48 patients by means of the combined intravesical instillation of thio-tepa and urokinase and in 28 patients through the instillation of thio-tepa alone. The recurrence rates of both therapies for the postoperative 18 months were 7.9 and 32.6 per cent, respectively, indicating a significant drop in the recurrence rate in the group subjected to the combined therapy. No significant difference was found between the 2 instillation groups in terms of the blood transmission of 32-P thio-tepa. Serious leukopenia was found in 2 of the 48 patients receiving the combined instillation therapy but we concluded that this was not attributable to the use of urokinase.

Topics: Adolescent; Adult; Aged; Carcinoma, Transitional Cell; Cystitis; Drug Therapy, Combination; Endopeptidases; Female; Hemorrhage; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Phosphorus Radioisotopes; Thiotepa; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Urokinase-Type Plasminogen Activator

Retrospective studies were carried out in 52 patients with polycythemia vera who were treated with radioactive phosphorus (32-P) over periods ranging between 4 and 24 years. Control of hematopoiesis was achieved in all patients. Duration of the remission induced differed considerably in the individual patients. Mean remission lasted 3-4 years. After 13 years of 32-P treatment, the mean duration of remission lengthened due to gradual transition of some cases into "spent" polycythemia. The mean annual dose of 32-P was about 2.4 mCi. In patients with long-term remissions, the dose accumulated per year was markedly less. These patients probably represent optimal preconditions for 32-P therapy. Mean survival was 12.5 years. The majority of the patients died from thorombo-embolie events or hemorrhage; incidence of acute leukemia was about 4%.

Topics: Acute Disease; Adult; Aged; Female; Hemorrhage; Humans; Leukemia; Male; Methods; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Radiotherapy Dosage; Remission, Spontaneous; Splenomegaly; Thromboembolism; Time Factors

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: Anemia, Hypochromic; Animals; Blood Transfusion; Carbon Radioisotopes; Cell Membrane; Cytoplasm; Erythrocytes; Hemoglobins; Hemolysis; Hemorrhage; Isotope Labeling; Microscopy, Electron; Osmotic Fragility; Phosphatidylethanolamines; Phosphorus Radioisotopes; Rats; Reticulocytes; Splenectomy; Stress, Physiological

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: Acute Disease; Bloodletting; Female; Hemorrhage; Humans; Leukemia; Male; Middle Aged; Minnesota; Phosphorus Radioisotopes; Polycythemia Vera; Pressure; Primary Myelofibrosis; Retrospective Studies; Sex Factors; Splenectomy; Splenomegaly; Syndrome