M. L. Randi

Leukemia and myelodysplasia effect of multiple cytotoxic therapy in essential thrombocythemia.

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by increased risk of thrombosis and/or hemorrhages. Cytotoxic drugs are mostly used in patients at high risk for thrombotic complications, while their use is still debated in low risk patients because of the risk of leukemia or secondary neoplasm. We discuss the leukemic risk of available treatment strategies in a large cohort of patients. Over a 12 years period we treated 23 patients with busulfan (BU), 1 with pipobroman (Pi), 6 with 32P, 48 with hydroxyurea (HU) in 62 cases associated with acetyl salicylic acid (ASA) while 77 patients received ASA alone and 33 did not receive any therapy. We observed 2 cases of acute leukemia (AL) and 1 of myelodysplastic syndrome (MDS). One of these patients had been treated with 32P and Pi these after with and the other two with BU and HU. They represented 23% of all patients treated with more than 1 cytotoxic agent, 16.6% of 32P treated subjects, 4% of those with HU and 6.4% of those with BU. The case of MDS occurred in a 81 years old female and represents 4% of cases of ET over the 70 years of age. No cases of AL or MDS were observed in patients not receiving cytotoxic therapy (with or without ASA). According to our experience the use of more than one cytotoxic agent in ET confirms the increase in the risk of leukemia in these cases. However, none of the patients treated with HU alone, even for more than 10 years (12 cases) developed AL. No treatment or therapy with ASA alone may be the best choice in young patients with ET with a low risk of thrombotic complications.

Thrombocytosis in young people: Evaluation of 57 cases diagnosed before the age of 40

SummaryOver the past 13 years 57 cases of primary thrombocytosis in young people have been studied. Only patients with a platelet count over 500×109/liter and a follow-up longer than 2 years were considered. Thrombocytosis in young people represents approximately 25% of total cases referred to our department during this period. The most common causes are essential thrombocythemia (20 cases) and secondary thrombocytosis (22 cases). The highest platelet counts are found in essential thrombocythemia patients. Most of our patients were discovered by a fortuitous hematological examination. In contrast, 5 out of the polycythemic patients were recognized after a thrombosis. The same was true for 2 out of 20 essential thrombocythemia subjects. Four subjects (2 essential thrombocythemia and 2 secondary thrombocytosis) were diagnosed after hemorrhages. The overall survival was very good except for leukemic patients and thrombocytosis secondary to neoplasms. Vascular complications after diagnosis were scarce: 2 polycythemia vera patients showed bleedings during antiaggregating therapy. None of our patients developed epithelial cancer, malignant lymphoma or myelofibrosis. Vascular traumata seem more frequent in polycythemia vera regardless of age. Therefore, it seems useful to treat polycythemic patients, while no therapy seems to be indicated in other forms of thrombocytosis.

The possible value of platelet aggregation studies in patients with increased platelet number

SummaryADP, adrenalin and collagen platelet aggregation studies were performed in 54 patients with elevated platelet counts: 38 patients showed primary thrombocythemia and 16 secondary thrombocytosis. Patients with primary thrombocythemia (78.7%) showed a decreased aggregation pattern while in patients with secondary thrombocytosis platelet aggregation response was entirely normal. An increase in platelet aggregation was obtained in four patients with primary thrombocythemia. The platelet aggregation response did not appear to be related to circulating platelet number. A relationship between increased platelet aggregation and the occurrence of thrombosis was demonstrated. Similarly, a correction between impaired platelet aggregation and bleeding was also present. These results emphasize the diagnostic value of platelet aggregation studies in patients with elevated platelet number.

Normal and low molecular weight heparins: interaction with human platelets

Abstract. Porcine mucosal heparin was chemically depolymerized. The depolymerization was stopped at different steps to obtain two low molecular weight (LMW) heparins with a molecular weight of 10 000 and 6000, respectively. The LMW heparins were tested in vitro for anti‐clotting activities and for platelet serotonin release in different systems in comparison with normal heparins, dermatan and heparan sulphate.

The significance of thrombocytosis in old age.

We performed a retrospective study on 21 patients, aged 70 years or more, affected by polycythemia vera (PV) or essential thrombocythemia (ET). As controls, we evaluated 10 younger ET patients. The results indicate that in older ET subjects there was a lower incidence of hemorrhagic and thrombotic complications than in younger patients and PV patients. However, platelet number and platelet function tests were similar in all the patients studied. We suppose that an increase in hematocrit as seen in PV is much more dangerous as compared to an isolated increase in platelet count, and that thrombocytosis alone in old age can be an isolated expression of a natural involution of blood marrow similar to myelofibrosis.

Plasma and Platelet Beta-Thromboglobulin Levels in Patients with May-Hegglin Anomaly

Plasmatic beta-thromboglobulin (BTG) has been assayed in 5 patients with May-Hegglin anomaly. All patients showed a normal BTG plasmatic level. The plasma BTG/number of platelets ratio resulted to be elevated but this was due to the low platelet count typical of the disease. The platelet content in BTG was studied in only 2 patients and was found to be four times the normal value; however, the circulating BTG platelet mass in these patients resulted to be within normal limits.

Effect of heparin and aspirin on platelet and clotting activation during leukapheresis

Abstract. β‐thromboglobulin (βTG), serotonin (5HT) and fibrinopeptide A (FPA) were assessed in twenty‐two normal donors before, during, and at the end of leukapheresis. Seven procedures were carried out adding heparin to the circuit, and seven adding acetyl salicylic acid (ASA). The remaining eight procedures were carried out using only citrate and served as controls. Plasma βTG increased both during and after the apheresis, together with a significant decrease of the intra‐platelet content. Platelet 5HT did not show significant changes whereas FPA increased significantly. Using heparin, we obtained a complete prevention of FPA cleavage during the entire procedure, while βTG increased at the middle of the procedure. No significant effects were observed using ASA both on βTG and FPA levels. These features clearly indicate the activation of platelets and the thrombin generation in the apheresis circuit. Nevertheless, the activation of the clotting system seems to be predominant, as supported by the improved effect of heparin on βTG and FPA amounts.

Increased Number of Pseudodrumsticks in Neutrophils and Large Platelets. A ‘New’ Congenital Leukocyte and Platelet Morphological Abnormality

2 members of a family, a child and his father, showed a combined morphological abnormality of leukocytes and platelets. The abnormality consisted of the presence of pseudodrumsticks in the neutrophils and of large platelets. One or more than one pseudodrumstick was present in about 40% of neutrophils. Leukocyte count, differential count and enzymatic stains were normal. Large platelets constituted about 25% of the platelet population. 1 patient also had mild thrombocytopenia which appeared to be unrelated to the basic defect since it appeared after a parotitis infection. Platelet function was normal but for a moderate prolongation of the bleeding time in the patient who had mild thrombocytopenia. No chromosomal abnormality was present in the propositi. The condition seems different from other leukocyte and platelet abnormalities so far described.

Abnormal Platelet Aggregation in Patients with Bartter’s Syndrome

Bartter’s syndrome is characterized by hypokalemia, hyperreninemia, hyperaldosteronism without hypertension, and juxtaglomerular cell hyperplasia.1 Recent studies have demonstrated an increase of the urinary excretion of prostaglandins (PGs) PGE2, PGF2α 2–4 and 6-keto PGF1α 5,6 in cases of Bartter’s syndrome.