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Background: Diagnoses from non-specific symptoms lead to reason over a huge space of hypotheses. Bayesian Networks (BN) can systematically address the task by integrating existing causal medical knowledge and clinical, possibly incomplete, case observations. Although prior specification of a causal BN structure can increase the generality of diagnostic predictions, particular care should be paid to avoid structural inconsistencies with the data at hand. Methods: The causal structure of a BN covering 129 cardiopulmonary disorders and 235 manifestations was elicited by experts. Markov chain Monte Carlo estimation of quantitative parameters was performed on the basis of 282 cases admitted to an Emergency Department and subsequently hospitalized. BN structural features underwent a refinement process to improve parameters sensitivity to data and diagnostic precision, until changes were consistent with published evidence. Discrimination/calibration measures of diagnostic performance (based on 284 test cases) were used to assess the predictive improvement after refinement. Results: Although one third of 1,417 parameter estimates remained anchored to prior settings, the BN updated by data returned adequately calibrated diagnostic predictions on the first six most observed disorders in the test sample, with an M-index of 0.91 (95% CI 0.87, 0.95) on 20 alternative diagnoses. Conclusions: Our large-sized BN effectively combines existing causal medical knowledge with sparse information contained in clinical records. It addresses a broad-spectrum differential diagnosis and informs physicians about possibly neglected cardiopulmonary conditions. The calibration analysis oriented the refinement of initial causal assumptions without loss of generality in diagnostic predictions.

A state‐of‐the‐art lecture titled “Myeloproliferative Neoplasm‐associated Thrombosis” was presented at the ISTH congress in 2021. We summarize here the main points of the lecture with two purposes: to report the incidence rates of major thrombosis in polycythemia vera and essential thrombocythemia and to discuss to what extent cytoreductive therapy and antithrombotic drugs have reduced the incidence of these events. Unfortunately, the incidence rate of thrombosis remains high, ranging between 2 and 5/100 person‐years. It is likely that new drugs such as interferon and ruxolitinib can be more efficacious given their cytoreductive and anti‐inflammatory activities. Despite prophylaxis with vitamin K antagonists and direct oral anticoagulants after venous thrombosis in either common sites or splanchnic or cerebral sites, the incidence rate is still elevated, as high as 4 to 5/100 person‐years. Future studies with new drugs or new strategies should consider thrombosis as the primary endpoint or surrogate biomarkers only if previously validated.

Clinical evidence supports the need of changing the diagnostic criteria of the 2008 updated WHO classification for polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). In JAK2-mutated patients who show characteristic bone marrow (BM) morphology, clinical studies demonstrated that a hemoglobin level of 16.5g/dL in men and 16.0g/dl for women or a hematocrit value of 49% in men and 48% in women are the optimal cut off levels for distinguishing JAK2-mutated ET from "masked/prodromal" PV. Therefore BM morphology was upgraded to a major diagnostic criterion. Regarding ET the key issue was to improve standardization of prominent BM features enhancing differentiation between "true" ET and prefibrotic/early primary myelofibrosis (prePMF). These two entities have shown a different epidemiology and clinical outcomes. Concerning prePMF a more explicit clinical characterization of minor criteria is mandated for an improved distinction from ET and overt PMF and accurate diagnosis and outcome prediction.

Bone marrow (BM) morphologic features remain the cornerstone of diagnosis in both essential thrombocythemia (ET) and polycythemia vera (PV). In addition, recently discovered mutations, such as JAK2, CALR, and MPL, have proven useful in facilitating the diagnostic process. A JAK2 mutation is expected in PV, and its absence makes the diagnosis unlikely. However, JAK2 mutations also occur in about 60% of patients with ET, which underlines the need for BM examination in distinguishing JAK2-mutated ET from PV when the hemoglobin/hematocrit level is diagnostically equivocal (ie, as in "masked" PV). Most patients with JAK2-unmutated ET express CALR or MPL mutations, with respective estimated incidences of 22% and 3%, while approxmately 15% are wild-type for all 3 mutations (ie, they are triple-negative). As such, CALR first, followed by MPL if CALR is absent, mutation screening is appropriate in the diagnostic work-up of JAK2-unmutated ET but does not replace the need for BM morphologic examination in (1) confirming the diagnosis in triple-negative ET and (2) distinguishing ET from other myeloproliferative neoplasms that share the same mutations, including masked PV and early/prefibrotic myelofibrosis. Young patients (aged < 60 years) with ET or PV and no history of thrombosis are conventionally regarded as having "low-risk" disease. First-line treatment in low-risk PV is phlebotomy to achieve a hematocrit target of 45% and low-dose aspirin, and first-line treatment in ET is observation alone in the absence of additional risk factors for arterial thrombosis (ie, JAK2 mutation and cardiovascular risk factors) or low-dose aspirin therapy, once or twice daily, in the presence of one or both of these risk factors, respectively. Cytoreductive therapy is indicated in high-risk (patients aged ≥ 60 years or a history of thrombosis) PV or ET in the form of hydroxyurea as first-line and interferon alfa or busulfan as second-line drugs of choice. We do not use ruxolitinib in patients with PV unless they have severe pruritus or symptomatic splenomegaly that is proved to be refractory to hydroxyurea, interferon alfa, and busulfan.

Because the current therapy in polycythemia vera (PV) and essential thrombocythemia (ET) is aimed at lowering the risk of thrombosis, the risk classification system in these disorders is shaped according to thrombotic risk. Patients with either PV or ET can be stratified in a "high-risk" or "low-risk" category according to their age and previous history of thrombosis. Whether novel risk factors such as leukocytosis and JAK2 mutation may be included in the prognostic stratification requires confirmation in prospective future clinical studies. The identification and appropriate management of cardiovascular risk factors and the promotion of a healthy lifestyle in chronic myeloproliferative neoplasms (MPN), as in the general population, should be considered a cornerstone of vascular prevention. Blood hyperviscosity in PV is a major cause of vascular disturbances which severely impact on morbidity and mortality. An aggressive target of hematocrit lower than 45% in males and 42% in females has been advised by the European LeukemiaNet (ELN) group, although no convincing evidence of this recommendation is currently available. The efficacy and safety of low-dose aspirin (100mg daily) in PV has been assessed in the European Collaboration on Low-dose Aspirin in Polycythemia (ECLAP) double-blind, placebo-controlled, randomized clinical trial. Translating evidence from the positive results of ECLAP to ET may be questionable. The most commonly used front-line therapy drugs for the treatment of high-risk PV and ET patients include hydroxyurea and alpha-interferon at any age while anagrelide is recommended as second line-therapy in resistant and intolerant ET patients. Busulphan is a front-line therapy in the elderly. By definition, children with ET are a population with low vascular risk unless a major thrombotic or hemorrhagic event has occurred. ELN recommends to prescribe cytoreductive drugs in children as a last resort. No results of clinical trials with JAK-2 inhibitor drugs in PV and ET are so far available.

The term RBC-transfusion-dependence is widely-used by hematologists to describe a condition of severe anemia typically arising when erythropoiesis is reduced such that a person continuously requires ≥ 1 RBC-transfusions over a specified interval. Defining a person as RBC-transfusion-dependent has important implications in diverse hematological disorders especially because it strongly-correlated with decreased survival. Conversely, becoming RBC-transfusion-independent or receiving fewer RBC-transfusions over a specified interval is defined as improvement or response in many disease- and/or therapy-setting. Whether this correlates with improved survival is controversial. We used a structured expert-panel consensus panel process to define RBC-transfusion-dependence and -independence or improvement. We suggest these definitions may prove useful to persons studying or treating these diseases.

The occurrence of hepatic veno-occlusive disease (VOD) has been reported in up to 60% of patients following stem cell transplantation (SCT), with incidence varying widely between studies depending on the type of transplant, conditioning regimen, and criteria used to make the diagnosis. Severe VOD is characterized by high mortality and progression to multiorgan failure (MOF); however, there is no consensus on how to evaluate severity. This review and analysis of published reports attempts to clarify these issues by calculating the overall mean incidence of VOD and mortality from severe VOD, examining the effect of changes in SCT practice on the incidence of VOD over time, and discussing the methods used to evaluate severity. Across 135 studies performed between 1979 and October 2007, the overall mean incidence of VOD was 13.7% (95% confidence interval [CI] = 13.3%–14.1%). The mean incidence of VOD was significantly lower between 1979–1994 than between 1994–2007 (11.5% [95% CI, 10.9%–12.1%] vs 14.6% [95% CI, 14.0%–15.2%]; P < .05). The mortality rate from severe VOD was 84.3% (95% CI, 79.6%–88.9%); most of these patients had MOF, which also was the most frequent cause of death. Thus, VOD is less common than early reports suggested, but the current incidence appears to be relatively stable despite recent advances in SCT, including the advent of reduced-intensity conditioning. The evolution of MOF in the setting of VOD after SCT can be considered a reliable indication of severity and a predictor of poor outcome.

The management of pregnancy in Philadelphia negative chronic myeloproliferative disorders (CMPDs) is an increasingly frequent problem. In the literature, most pregnancies are reported for women with essential thrombocythemia (ET) with about 400 pregnancies in about 200 women. In ET, first trimester abortion is the most frequent complication occurring in about one third of pregnancies. Interestingly, the incidence of maternal complications is relatively low with 3% for major thromboembolic and 2% for major bleeding events. The presence of the Jak2 mutation seems to be an independent predictor of pregnancy complications. Pregnancies in ET should be stratified according to underlying risk factors in low, high and highest risk pregnancies. Women with low risk pregnancies are treated with low-dose aspirin, whereas women with high and higher risk pregnancies may benefit from low-dose aspirin plus interferon alpha +/- low molecular weight heparin throughout pregnancy and at least for six weeks post-partum. In polycythemia vera (PV) there is only very few information on pregnancy outcome with 36 pregnancies reported in the literature. According to these data pregnancy in PV is per se a high risk situation. Accordingly, all women with PV should be treated with low-dose aspirin. Some pregnant PV patients may benefit from a more intensive therapy including interferon alpha +/- low molecular weight heparin throughout pregnancy and at least for six weeks post-partum.

Clinical studies suggest a survival advantage in cancer patients receiving low molecular weight heparin (LMWH). A suggested mechanism for this beneficial effect may reside in the antiangiogenic activity of heparins.In this study we investigated whether two different LMWHs, i.e. enoxaparin and dalteparin, and unfractionated heparin (UFH), affect the angiogenic potential of human microvascular endothelial cells (HMEC-1) promoted by tumor cells.HMEC-1 cells were incubated with tumor cell conditioned media (TCM) derived from human breast cancer and leukemic cells (i.e. MCF-7, MDA.MB.231, and NB4 cell lines) or recombinant cytokines (i.e. VEGF, FGF-2, TNF-alpha) +/-heparins. Capillary-like tube formation in Matrigel and cell proliferation were evaluated.All three TCM induced a significant (p0.05) increase in total length of tubes formed by HMEC-1 in Matrigel. These increases were significantly counteracted (62 to 100% mean inhibition) by enoxaparin and dalteparin, but were significantly less affected by UFH. Similarly, the tube formation induced by standard VEGF, FGF-2, or TNF-alpha was 100% inhibited by enoxaparin, and 70-90% by dalteparin, whereas minor or no inhibition was observed with UFH. VEGF was the most active cytokine in TCM of both breast cancer and leukemic cells. EC proliferation was significantly increased by standard angiogenic factors, and slightly affected by breast cancer TCM (p=ns). The addition of heparins significantly counteracted the proliferative stimuli.These results support a major role for LMWH compared to UFH in inhibiting the proangiogenic effect exerted by tumor cells or purified angiogenic factors on microvascular endothelium.

Purpose The risk of recurrent venous thromboembolism (VTE) in patients with polycythemia vera and essential thrombocythemia has been scarcely addressed, and whether long-term oral anticoagulant treatment or acetylsalicylic acid should be recommended after first occurrence of deep venous thrombosis (DVT) is unknown. This multicenter cohort study was aimed to assess the rate of recurrent VTE in patients with polycythemia vera or essential thrombocythemia in comparison with a control group of individuals with previous VTE and without neoplastic diseases. Patients and Methods We retrospectively estimated the rate of recurrence in 79 patients with myeloproliferative disorders (MPDs; polycythemia vera/essential thrombocythemia, 45/34) and with a previous proximal DVT. Patients were divided into 2 groups. The first comprised 41 patients who received acetylsalicylic acid after 6 months of oral anticoagulant treatment. The second group was composed of 38 patients given long-term oral anticoagulant treatment without acetylsalicylic acid. The majority of patients were treated with cytotoxic drugs. The results were compared with the recurrences seen in 176 patients without cancer with previous proximal DVT given short-term oral anticoagulant treatment. Results In the patients with polycythemia vera and essential thrombocythemia, the rate of recurrent DVT was higher in the group receiving acetylsalicylic acid (32%) compared with the group on oral anticoagulant treatment (16%), although not statistically significant. The rate of recurrent DVT in MPD cases receiving acetylsalicylic acid was quite similar to that of patients without cancer (33%). The cumulative probability of recurrent VTE indicated a trend of fewer events in the MPD cases on long-term oral anticoagulant treatment. In the patients with MPDs, the incidence of major bleeding during oral anticoagulant treatment or acetylsalicylic acid was 1% and 0.5% patient-years (years of observation), respectively. Conclusion This retrospective analysis would suggest a long-term oral anticoagulant treatment after a first DVT in patients with polycythemia vera and essential thrombocythemia. However, this indication should be weighed against the risk of major hemorrhagic events that seems lower during long-term prophylaxis with acetylsalicylic acid. Therefore, a prospective clinical trial comparing acetylsalicylic acid in patients with polycythemia vera and essential thrombocythemia with oral anticoagulant treatment in the prevention of recurrent VTE is warranted.

Bleeding and thrombosis are major risk factors for early death in patients with acute leukemia; chemotherapy increases the likelihood of both of these complications. Patients with acute leukemia often present with a hypercoagulable state or with evidence for chronic disseminated intravascular coagulation, even in the absence of active thrombosis and/or bleeding. Leukemic cell procoagulant properties, cytotoxic therapies, and concomitant infections are major determinants of clotting activation in acute leukemia. Clinical manifestations range from localized venous or arterial thrombosis to diffuse life-threatening bleeding. All-trans retinoic acid has greatly improved the management of acute promyelocytic leukemia, but has not significantly changed the rate of early hemorrhagic deaths and may actually promote thrombosis. Randomized, controlled trials of different prophylactic regimens to prevent thrombosis and/or bleeding in acute leukemia are urgently needed, particularly in patients with acute promyelocytic leukemia. Anticoagulant therapy is a unique challenge in patients with acute leukemia, who are at high risk for hemorrhage. Although no guidelines are available for prophylaxis or treatment of thrombosis, extrapolation can be made from existing guidelines for management of patients with other malignancies prolonged periods of treatment-induced thrombocytopenia in patients with acute leukemia, however, require a more judicious application of standard anticoagulant approaches. Use of the newer anticoagulants will require careful assessment of hemorrhagic risk in this group of high risk patients but may be justified under special circumstances.

The clinical course of polycythemia vera is marked by a high incidence of thrombotic complications, which represent the main cause of morbidity and mortality. Major predictors of vascular events are advanced age and previous thrombosis. Myelosuppressive drugs can decrease the rate of thrombosis, but there is concern that their use increases the risk of transformation into acute leukemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Patients at low risk should be treated with phlebotomy and low-dose acetylsalicylic acid. Cytotoxic therapy is indicated in patients at high risk, and the drug of choice is hydroxyurea because its leukemogenicity is low. The recent discovery of JAK2 (V617F) mutation in the vast majority of patients with polycythemia vera opened new avenues for the treatment of this disease. Novel therapeutic options theoretically devoid of leukemic risk, such as interferon-α and imatinib, were found to affect JAK2 expression in some patients. However, these drugs require further clinical experience and, for the time being, should be reserved for selected cases.

The clinical course of polycythemia vera is marked by significant thrombotic complications and a variable risk of the disease turning either into myeloid metaplasia with myelofibrosis or into acute myeloid leukemia. Cytoreductive treatment of blood hyperviscosity by phlebotomy or chemotherapy and antiplatelet therapy with low-dose aspirin have dramatically reduced the number of thrombotic complications and substantially improved survival. However, there is concern that certain myelosuppressive drugs accelerate the disease progression to acute leukemia. Thus, the objective of management is two-fold: first, to minimize the risk of thrombotic complications; second, to prevent progression to myelofibrotic or leukemic transformation. This chapter provides updated estimates of the risk of thrombosis and disease progression and evaluates the various randomized and observational studies in polycythemia vera, according to an evidence-based approach.

Although far from perfect, randomized clinical trials (RCTs) are the best mechanism available for evaluating the risk/benefit profile of a particular therapy. Given this, it is particularly unfortunate that there have been few clinical trials of therapy for myeloproliferative diseases (MPDs) as these therapies are often based on agents with unclear long-term safety. A complex profile of MPD uncertainties requires a simple, but articulated strategy of care and research to allow a reasonable transfer of the best available validated knowledge and a timely investigation of the most relevant questions. The multi-country, collaborative RCTs are key to generating valid data. The prerequisite for success is the close interaction of the clinical community and the research community studying the same patients. Data to be collected, criteria, contents, frequency of follow-up, and documentation of the events should be as similar as possible to those used in routine clinical care. One of the greatest achievements of the multicenter trials with this orientation has been to produce a "core" of data and practices, on which the main analyses will be made, but which at the same time reflect an optimal level of patient care for the majority of patients.

Essential thrombocythemia, polycythemia vera, and myelofibrosis with myeloid metaplasia constitute the "classic" bcr/abl-negative myeloproliferative disorders (MPDs). Each of these MPDs represents a stem cell-derived clonal myeloproliferation with the respective features of thrombocytosis, erythrocytosis, and bone marrow fibrosis. Unlike with cases of chronic myeloid leukemia, in which the bcr/abl mutation is invariably detected, current diagnosis of essential thrombocythemia, polycythemia vera, and myelofibrosis with myeloid metaplasia is based on a consensus-driven set of clinical and laboratory criteria that have undergone substantial modification in recent times. The recent discovery of a recurrent activating Janus tyrosine kinase (JAK2) mutation (JAK2VG17F) in all 3 classic MPDs offers another opportunity for refining current diagnoses and disease classifications. In this article, we outline contemporary diagnostic algorithms for each of these disorders and provide an evidence-based approach to management.

The clinical course of Polycythemia vera (PV) and Essential Thrombocythemia (ET) is marked by an high incidence of thrombotic complications, which represent the main cause of morbidity and mortality. Major predictors of vascular events are increasing age and previous thrombosis. Myelosuppressive drugs can reduce the rate of thrombosis, but there is concern that their use raises the risk of PV and ET transformation into acute leukemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Low-risk patients with PV should be treated with phlebotomy and low-dose aspirin, whereas those with ET can be left untreated. Cytotoxic therapy is indicate in high-risk patients and the drug of choice is hydroxyurea because its leukemogenicity is low, if any. New therapeutic options, theoretically devoid of leukemic risk, such as alpha-interferon, anagrelide and imatinib should be reserved to selected patients and require further clinical experience.

Antiphospholipid antibodies, i.e. lupus anticoagulants and anticardiolipin antibodies, are associated with obstetric complications. Fetal death and recurrent spontaneous abortions represent the obstetric criteria of the antiphospholipid syndrome. They occur with similar frequences and have an overall prevalence of 15-20%. Lupus anticoagulants carry a risk 3.0 to 4.8 times, and anticardiolipin antibodies 0.86 to 20 times higher than controls. The mechanism(s) by which antiphospholipid antibodies cause these events still has to be defined: thrombosis in the placental vessels, and impairment of embryonic implantation have been proposed. Unfractionated or low-molecular-weight heparin, alone or in combination with low-dose aspirin, represent the current standard treatment of pregnant antiphospholipid-positive women for preventing recurrent obstetric complications. Upon treatment, the live birth rate increases from 0-40% to 70-80%. However, there is still an excessive frequency of maternal and/or fetal complications, indicating the necessity of a better calibration of the dosage, duration and timing of administration of heparin treatment.

Essential thrombocythemia (ET), one of the chronic myeloproliferative disorders, exposes individuals to significantly increased risk for thrombohemorrhagic complications. Epidemiologic data indicate that the two most prominent risk factors for thrombosis are age greater than 60 years or a history of or presentation with thrombosis at any age. Age is an important factor in selecting among therapeutic options, as the agents used to treat ET may contribute to acute leukemic transformation and other secondary malignancies. Whether or not hydroxyurea (HU) carries these risks is controversial and unresolved, but the uncertainty is a basis for avoiding it in young patients. Alternatives to HU that have established efficacy in lowering platelet counts in ET are interferon and anagrelide. Both are highly effective in reducing platelet numbers, and are apparently not associated with leukemogenicity or mutagenicity. However, approximately 30% of patients find interferon intolerable for long-term therapy. Anagrelide offers the advantage of oral dosing and long-term effectiveness at managing platelet counts. A recent long-term study of young ET patients treated with anagrelide found that all thrombohemorrhagic events occurred in patients with platelet counts greater than 0.4 × 10 9 /L, adding to the evidence that reduction of platelet counts to normal may be required for optimal control of risk. Semin Hematol 40(suppl 1):22-25. © 2003 Elsevier Inc. All rights reserved.

sOncologia,Ospedale 'Infermi', Rimini, Italy Summary Background: The definition of prognostic parameters in early stages of gastric lymphoma is still controversial. The aim of this retrospective analysis was to assess the value of the stagemodified international prognostic index (IPI) in predicting the outcome of a large, consecutive series of patients with PGL of diffuse large B-cell histology (DLCL). Patients and methods: Three hundred twelve consecutive, newly-diagnosed, patients with localized PGL (stages I-IIE according to the 'Lugano staging system for GI lymphomas') referred from April 1972 to December 1997 to eight Italian and one Swiss centers were reviewed and their outcomes updated to June 1998. One hundred three patients were treated with single-modality therapy, while two hundred four received combined-modality treatment, most of which included surgery and short-term chemotherapy. Results: After a median follow-up of 66 months (range 0.6300 months), 195 (64%) were alive in first continuous complete remission (CCR). The five-year estimates of overall survival (OS) and event-free survival (EFS) were 75% and 67%, respectively. OS and EFS varied according to IPI, from, respectively, 90% and 82% for patients with 0-1 risk factors, to 40% and 35% for patients with ^3 risk factors (P = 0.00001). Cox regression analysis showed that IPI was the strongest predictor of survival. Conclusions: This study shows that stage-modified IPI is an effective predictive model in patients with primary DLCL of the stomach, enabling identification of patients with significantly different outcomes.

3. Risk stratification of patients with ET . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258 3.1. Bleeding and thrombosis in ET . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258 3.2. Risk factors for major bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259 3.3. Risk factors for thrombosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259

purpose: The purpose of this study was to determine the incidence of hemostastic complications in young patients with essential thrombocythemia (ET). patients and methods: The clinical course of 44 patients under the age of 45 with the diagnosis of ET was reviewed in a retrospective manner. Patients were collected from three medical centers in the United States and Italy: the Brigham and Women's Hospital and the Harvard Community Health Plan, Boston, Massachusetts, and the Ospedali Riuniti di Bergamo, Bergamo, Italy. results: The overall incidence of hemorrhage or thrombosis, or both, in this group of patients was 39% (17 of 44), with serious complications occurring in 23% (10 of 44). Two patients died of thrombotic events. Neither the presence of symptoms at diagnosis nor any single laboratory parameter proved predictive of clinical sequelae. Treatment with antiplatelet drugs or platelet-lowering agents was not protective. conclusion: We conclude that ET in young patients may result in serious and life-threatening hemostatic problems and consequently that young age is not a favorable prognostic factor in this disease.

Procoagulant activity of peripheral blood mononuclear leucocytes was studied in 24 consecutive patients with Hodgkin's disease. Mononuclear cells, tested immediately after isolation, expressed very low activity which was, however, somewhat higher than that of cells from a matched control group (P = 0.063). Procoagulant activity generated by patients' mononuclear cells following stimulation with bacterial endotoxin was significantly higher than that produced by control cells (P less than 0.01). There was no apparent relation between procoagulant activity and pathological staging. The increased capacity of mononuclear phagocytes to produce procoagulant activity might help explain activation of blood coagulation and subsequent fibrin deposition in patients with Hodgkin's disease.

Several investigators have suggested that hairy cells are neoplastic B lymphocytes. These cells, however, also share some biological properties with mononuclear phagocytes. A property of these cells is the capacity to generate procoagulant activity (PCA) in response to a variety of stimuli. In this study we investigated the PCA of peripheral blood hairy cells in 19 consecutive patients with hairy cell leukaemia (HCL). Monocyte-depleted blood mononuclear cells, tested immediately after isolation, expressed little, if any, activity. However, after exposure to endotoxin, a marked increase in PCA was observed (42.1 ± 8.7 vs 1.3 ± 0.2 units/5 × 10 4 hairy cells). A significant correlation was found between the number of lymphocytes/hairy cell and the level of endotoxin-induced PCA suggesting that lymphocytes potentiate the procoagulant response of hairy cells. When stimulated with 12-0-tetradecanoyl-phorbol-13-acetate (TPA), patients' cells produced about 2–8 times more PCA than endotoxin-stimulated cells. The PCA induced by endotoxin and TPA was identified as tissue factor. These findings suggest some further relationship between hairy cells and monocytes.

The relation among lupus anticoagulant (LAC), anticardiolipin antibodies (ACA), and repeated abortions was evaluated in a case-controlled study of 49 women with two or more unexplained spontaneous abortions (cases) compared with 141 control subjects, who had had one or more normal pregnancies and no previous spontaneous abortion. The women were admitted to the same hospital where the cases had been identified for acute conditions other than immunologic neoplastic, gynecologic or cardiovascular. LAC was detected in 7 out of 49 cases (14%, 95% confidence limits 8% to 26%) but in none of the 141 controls. Similarly, ACA were detected in four cases (8%, 95% confidence limits 0.3% to 30%) but no controls. These differences in frequency were statistically significant. These findings confirm that LAC and ACA are associated with a history of repeated abortions in clinically asymptomatic patients for immunologic conditions.

A recently described platelet coagulant activity (factor X activating activity) was studied in two patients with essential thrombocythaemia and ten with polycythaemia vera. It was markedly reduced in the five patients with bleeding tendency, and also reduced in one patient with a history of peripheral ischaemia. It was either normal or increased in patients with no haemostatic complications. In the two subjects with lowest activity (five and thirteen percent) and most serious bleeding, chemotherapy resulted in normalisation of the platelet count and of platelet coagulant activity and in disappearance of the bleeding episodes. Our results suggest an association between bleeding tendency and reduced platelet coagulant activity. These findings may be of relevance to 1) the pathogenesis of abnormal bleeding in patients with myeloproliferative disorders and 2) the understanding of the role of platelet coagulant activities other than platelet factor 3 in disturbed haemostasis.

A series of 101 consecutive patients with chronic myeloproliferative disorders including polycythaemia vera, chronic myelogenous leukaemia, idiopathic myelofibrosis and essential thrombocythaemia have been studied. The aim was to establish the incidence of thrombotic and haemorrhagic complications and the possible role played by platelet number and function. The total incidence of haemostatic complications was 21% and the platelet functional tests investigated (platelet aggregation, generation of malondialdehyde, endogenous serotonin, beta-thromboglobulin and platelet coagulant activity) were of little help for predicting these clinical complications.

Platelet function was assessed in 17 patients with hairy cell leukemia who had undergone splenectomy. Defective PAF-induced aggregation and selective reduction of β-thromboglobulin were found in platelets from six and eight patients respectively. These defects were not necessarily associated with bleeding complications.