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Introduction: The management to reduce risk of thromboembolic complications in polycythemia vera and essential thrombocythemia are well established, but for other conditions with elevated hemoglobin, hematocrit, or platelets there are no consensus regarding treatment and follow up., Aims: To assess frequency of elevated blood values in patients with thromboembolic event, how many of these should be investigated further regarding myeloproliferative neoplasm and if the risk of recurrent event is depending on underlying condition., Methods: Retrospective cohort study of 3931 adult patients in the county of Norrbotten, Sweden, with thromboembolism during 2017 and 2018., Results: Of the 3931 patients, 1195 had either elevated Hb, HCT, or platelets fulfilling the 2016 revised WHO criteria for PV and ET, and out of these 411 should be evaluated regarding underlying myeloproliferative neoplasms. Unexplained thrombocytosis and secondary erythrocytosis were associated with the highest rate of recurrent event as well as the most inferior restricted mean survival time., Conclusion: Elevated blood values are common in patients with thromboembolic event and the high risk of recurrent event and inferior restricted mean survival time in patients with unexplained thrombocytosis and secondary erythrocytosis implicates the importance of finding and managing the underlying condition., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Controversies still exist regarding definition of the thrombotic risks in Ph- (BCR/ABL1-) myeloproliferative disorders with thrombocythemia (MPD-T). Platelet counts at diagnosis are currently not taken as a risk factor of thrombosis. In our cohort of 1179 patients with MPD-T, prospectively registered for anagrelide treatment, we found that the median platelet count prior to the thrombotic event was significantly higher than at time points without any ensuing thrombosis (453 vs. 400 × 10(9)/L, P < 0.001), albeit higher platelet counts at diagnosis tended to be connected with fewer thrombotic events (in contrast to WBC counts at diagnosis). The JAK2(V617F) mutation predicted both arterial and venous events, while age >65 yr, hypertension, diabetes mellitus, smoking, elevated triglyceride and homocysteine levels predicted arterial events only. For venous events, the specific thrombophilic risk factors (factor V 'Leiden' and others), antiphospholipid antibodies, and elevated factor VIII levels played a major role. During anagrelide treatment (± aspirin), we documented a decrease in both venous (6.7-fold) and arterial events (1.8-fold), while bleeding (mostly minor events) increased twofold compared to history. Our results suggest that keeping platelet counts at low levels may be a meaningful therapeutic measure to prevent thrombosis, although their counts at diagnosis lack any prognostic value., (© 2015 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.)

Background and Objectives: Fundus lesions can be the accompanying symptom in many hematological diseases. In cases of anemia or thrombocytopenia, the exact mechanism leading to fundus abnormalities is not completely understood. The aim of this study was to calculate the prevalence of fundus lesions in anemic and thrombocytopenic patients, and define the risk factors for retinopathy., Design and Methods: This cross-sectional study involved 226 patients with anemia and/or thrombocytopenia and a control group of 47 age-matched subjects. The studied variables were age, gender, hemoglobin levels, mean cell volume (MCV), red cell distribution width coefficient variation (RDW-CV), the type of onset of anemia, platelet counts, mean platelet volume (MPV), platelet distribution width (PDW), the platelet-large-cell ratio (P-LCR), prothrombin time (PT) and partial thromboplastin time (PTT)., Results: Retinopathy was observed in 28.3% of the patients as a whole, the presence of fundus lesions being closely associated with severe anemia (Hb < 8 g/dL) and severe thrombocytopenia (PLT < 50 x 109/L). Among the patients with concomitant anemia and thrombocytopenia, the incidence of retinopathy was 38%. Age, low hemoglobin levels, platelet counts, RDW-CV, and increased MCV, MPV and P-LCR were all significantly associated with the presence of fundus lesions at univariate analysis., Interpretation and Conclusions: Retinopathy is a frequent finding in anemic and thrombocytopenic patients, although it is often not significant clinically. As retinal hemorrhages were found in all of the patients with concomitant severe anemia and thrombocytopenia, it is recommended that all such patients undergo routine fundus examinations.

Myelofibrosis with myeloid metaplasia (MMM) usually affects older people and is associated with a median survival of 3.5-5 yr. Survival of MMM patients 55 yr old or younger is longer, but there is no information on the youngest subset. The presenting features, evolution and survival were analyzed in 9 patients with MMM aged 30 yr or less, representing 2.8% of two series including 323 cases. Age ranged from 17 to 30 yr; 3 patients were males and 6 females. Five patients were asymptomatic and none had constitutional symptoms. Anemia was observed in 4 patients, being severe in only one. The WBC count was normal in 7 patients and 2 had mild leukocytosis; moderate thrombocytosis was observed in 7 patients. No patient showed blood blast cells or bone marrow cytogenetic abnormalities. With a median follow-up of 6.8 (range 0.8-28) yr, 2 patients died 10.7 and 9.9 yr from diagnosis, one from complications of bone marrow transplantation performed after progression of the disease and the other from gastrointestinal bleeding secondary to portal hypertension. Among remaining patients, one developed Budd-Chiari syndrome, another was lost to follow-up at 3 yr, and 5 remain asymptomatic and currently without treatment (one had been splenectomized at diagnosis). These results indicate that in most young adults with MMM the disease presents without adverse prognostic factors and may remain stable for years, which may be of interest when considering the treatment of such patients.

For 366 patients with polycythaemia vera (PV) or essential thrombocythaemia (ET) diagnosed 1971-1990, oral administration of 32-P was used as myelosuppressive treatment. Retreatment was not restricted to any defined interval and the number of treatments or the total dose were not limited. For 107 patients, follow-up was > 10 years. 15 of these presented with life-threatening occlusive vascular symptoms and their survival was short. For the remaining 92 patients 5-yr survival was not significantly worse than for a Swedish population matched for age and sex. Survival at 10 yr was lower, 51% versus 66% expected. Acute myeloid leukaemia (AML) was diagnosed in 11 of the 107 patients (10.3%). In the whole material of 366 patients, 17 have developed AML with a median time of 8.5 yr from start of treatment. There was a maximum incidence of 4% per yr after 8-12 yr. Later, the incidence decreased. The median annual dose of 32-P for the AML patients was 100 MBq and was not significantly larger than for a matched control group surviving without AML, 96 MBq. The results are compared with reports on PV or ET patients treated with busulphan (Bu) or hydroxyurea (HU). With comparable periods of follow-up there are no indications that an adequate myelosuppression with oral 32-P will be associated with shorter survival or higher incidence of AML than treatment with Bu or HU. It is concluded that, for the time being, oral administration of 32-P is an acceptable standard treatment in PV and ET.

Platelet aggregation (PA) induced by ADP, collagen and epinephrine, plasma levels of beta-thromboglobulin (beta TG) and thromboxane B2 (TXB2) and serum TXB2 generation were studied in 11 patients with primary thrombocytosis (7 with essential thrombocythaemia and 4 with polycythaemia vera) and compared with 16 healthy subjects. 5 patients suffered from peripheral vascular ischaemia and another 3 had venous thrombosis, but none had bleeding complications. The patients showed an abnormal pattern of platelet function and of thromboxane generation distinct from the healthy subjects in three aspects. a) Shape change was 5-26 times greater, the lag-time of collagen PA was 2.3-2.9 times longer and the extent of epinephrine PA was nil or very low. ADP- or collagen-induced PA was also reduced (p less than 0.02). b) Plasma TXB2 generation (corrected to a normal platelet concentration) stimulated by the three PA inducers was within the range of the healthy subjects in spite of the reduced extent of PA. c) Plasma beta TG level and serum TXB2 generation (both corrected to a normal platelet concentration) were 2.9-7.1 times higher (p less than 0.001) indicating enhanced in vivo platelet activation and possibly increased thrombin generation. These abnormalities were not detected in another 4 patients with secondary thrombocytosis. The abnormal pattern of platelet function and thromboxane generation can be a useful laboratory method in the evaluation of patients with primary thrombocytosis. It might also explain the thrombotic complications which occurred in 8 of the patients in a manner such that increased or normal TXB2 generation overcomes the reduced extent of PA. In this respect, the pronounced serum TXB2 synthesis might be a marker of intravascular thrombosis.

71 patients with systemic lupus erythematosus (SLE) were studied for the occurrence of platelet antibodies by immunoblotting. Binding of IgG antibodies to platelet protein antigens was observed in 39 of the 71 patients. The most frequently detected and exceptionally strongly reacting antibodies were directed against platelet protein antigens with an approximate molecular weight of 65 kDa under nonreducing conditions. These antibodies were autoreactive and, when followed, they usually persisted. Interestingly, in this group of well-defined SLE patients, platelet antibodies against the most common targets (65 kDa) were significantly associated with the lupus anticoagulant, a history of thrombocytopenia and thrombosis, particularly with arterial occlusions. The lupus anticoagulant, on the other hand, correlated significantly only with venous thrombosis. In addition to the lupus anticoagulant, platelet antibodies against this unknown platelet protein may thus be a marker of a higher risk of thrombosis in SLE patients.