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The prognostic information provided by platelet counts was studied in 1115 patients with primary lung cancer and in 550 control patients with benign lung disorders. Patient records were retrospectively reviewed regarding histological tumour type, TNM stage, thromboembolic episodes and survival. The prevalence of thrombocytosis (platelet count > 400 x 10(9)/l) in patients with lung cancer was 32.1% vs. 6.4% in controls (p < 0.0001). Platelet counts increased with TNM stage (p < 0.0001). Patients with thrombocytosis had a shorter survival than patients with normal platelet count (p < 0.0001). Thrombocytosis was a predictor of short survival also when adjusted for tumour type, sex, age, and TNM stage (p < 0.001). The platelet count and the frequency of thrombocytosis declined after tumour resection (p < 0.0001). Thrombocytosis was not associated with thromboembolism. In conclusion, thrombocytosis is a clinically significant prognostic indicator regarding survival in patients with primary lung cancer.

An unusual cause of "hyperkalaemia" was observed in a neurosurgical patient admitted to our intensive care unit. The cause of the hyperkalaemia was not known initially and treatment with cation ion exchange resin was initiated to lower the elevated serum potassium level. The concurrent occurrence of thrombocytosis and hyperkalaemia raised the possibility of psuedohyperkalaemia associated with thrombocytosis. Simultaneous measurement of plasma and serum potassium with the Hitachi 917 Analyzer (indirect ion selective electrode, coefficient of variation = 1% to 2%) confirmed the diagnosis. Correlation between thrombocytosis and pseudohyperkalaemia was found to be highly significant (r = 0.54; P = 0.014). It is estimated that for for every 100 x 10(9)/L of platelets, an increase of 0.07 to 0.15 mmol/L of potassium is expected. In thrombocytosis, plasma rather than serum potassium should be measured.

Background: Although the distinction between clonal and reactive thrombocytosis is clinically relevant because clonal thrombocytosis has more thrombohemorragic complications, the differential diagnosis of these two entities can be difficult. Methods such as the detection of unstimulated erythroid or megakaryocyte colony growth are not readily available. Therefore, we measured blood thrombopoietin levels to determine whether these levels can be used to distinguish the two conditions., Patients and Methods: Thrombopoietin levels were measured in 73 patients with thrombocytosis (platelet count > 500,000/microL), including 39 patients with clonal thrombocytosis (20 patients with essential thrombocythemia, 15 with agnogenic myeloid metaplasia, 1 patient with polycythemia vera, and 3 with undefined myeloproliferative disorders) and 34 patients with reactive thrombocytosis (17 with malignant tumors, 11 with inflammatory diseases, 4 with sickle cell disease, and 2 with iron deficiency anemia). Seventeen normal volunteers were used as controls., Results: Thrombopoietin levels were significantly higher (P < 0.05) in patients with clonal thrombocytosis (mean +/- SD of 555 +/- 585 pg/mL), including the subgroup with essential thrombocythemia (505 +/- 459 pg/mL), than in patients with reactive thrombocytosis (290 +/- 133 pg/mL) who had similar levels as controls (201 +/- 112 pg/mL). Thrombopoietin levels in patients with clonal thrombocytosis, including essential thrombocythemia, were not correlated with platelet counts., Conclusions: Thrombopoietin levels may be helpful in distinguishing between clonal thrombocytosis and reactive thrombocytosis. Thrombopoietin is probably responsible for the elevated platelet counts in clonal thrombocytosis including essential thrombocythemia, but not in reactive thrombocytosis. High thrombopoietin levels in patients with clonal thrombocytosis cannot be explained solely by platelet megakaryocyte mass.

A 10.5-year-old, castrated male shih tzu was presented for evaluation of weakness, pica, and pallor of the mucous membranes. A hemogram indicated an inflammatory leukogram and a regenerative anemia with spherocytosis and thrombocytosis. The dog responded well to conservative therapy for immune-mediated hemolytic anemia (IMHA). However, the thrombocytosis did not resolve. Serial hemograms were characterized by persistent thrombocytosis (platelet count, 577,000 to 1,200,000/microl) with abnormal platelet morphology. A systematic investigation ruled out causes of physiological and reactive thrombocytoses. A diagnosis of essential thrombocythemia was made by fulfilling the criteria of the Polycythemia Vera Study Group of the National Cancer Institute. The marked thrombocytosis was nonresponsive to hydroxyurea therapy. The dog remains healthy despite the marked increase in the number of circulating platelets. A review of causes of thrombocytoses in humans and animals is presented, and the criteria for diagnosis of essential thrombocythemia are examined.

We describe a case of essential thrombocythemia (ET), presenting as digital gangrene. ET is a rare myeloproliferative disorder characterised by a persistently elevated platelet count which commonly presents with haemorrhagic manifestations. Thrombosis occurs less frequently and digital gangrene is an uncommon presentation.

A case is described of acute leukosis presenting with unusual clinical picture. In a female patient aged forty nine presenting with signs of diabetes insipidus, blood count revealed thrombocytosis together with alterations suggesting acute leukosis. Bone marrow blasts showed the typical morphological features of megakaryoblasts. Institution of chemotherapy made for dispelling of diabetes-insipidus manifestations. To the authors' thinking, they observed a rare megakaryoblastic variety of acute leukosis caused by leukotic infiltration of the hypothalamohypophyseal zone in a patient wasted by heavy urination as is common in diabetes insipidus.

Differential diagnosis of thrombocytosis is not always obvious. The routine clinical chemistry laboratory classically provides only limited help in distinguishing between reactive thrombocytosis (RT) and autonomous thrombocytosis, where platelet production escapes normal regulatory processes, and which is seen in myeloproliferative diseases (MPD) such as essential thrombocythemia and polycythemia vera. We explored the clinical use of platelet distribution width (PDW) in the differential diagnosis of thrombocytosis. During a 3-month period, 250 patients presenting with a platelet count > 500 x 10(9)/L were studied; 174 were classified as having RT, 42 had a diagnosis of MPD, and 34 patients were excluded because they had a hemopathy different from MPD, and either did or did not present a known etiologic factor for RT. First, we determined that in the RT group the value of PDW was closely linked to both mean platelet volume (MPV) and platelet count (PLT) (PDW = 79.5-0.005 PLT -3.5 MPV; r = 0.848, R2 = 0.720). Therefore a new parameter, PDWresidual was defined (PDWresidual = PDWobserved -PDWexpected). Second, the discrimination between reactive and autonomous thrombocytosis obtained with PDWresidual was compared with that obtained with either PDW, MPV, or PLT. PDWresidual provided much more powerful than each of the other parameters used separately: 76% of MPD patients had a PDWresidual above the 95th percentile value of the RT population and none of the MPD patients had a PDWresidual below the 50th percentile. Thus, the combined interpretation of PLT, MPV, and PDW through the use of a PDWresidual appears highly useful in the differential diagnosis of thrombocytosis. Also, through simple modeling, more information can be drawn from parameters such as PDW that hitherto were mostly discarded as being without clinical interest.

Essential thrombocythemia is a rare disease of unknown etiology characterized by an abnormal increase in the platelet count which cannot be explained by other identifiable causes such as malignancy, infection, chronic inflammatory diseases or other myeloproliferative disorders. It rarely affects people less than 50 years of age and may be associated with hemorrhagic or thrombotic tendencies. A care of pregnancy complicated by essential thrombocythemia treated with aspirin, antiaggregating agent, throughout pregnancy and with hydroxyurea, a platelet lowering drug is reported. Also examine are some pathogenetic and therapeutic aspects of the thrombotic tendency secondary to elevated platelet count in pregnancy.

A girl with neurofibromatosis type 1 showed in infancy extreme thrombocytosis with platelet counts exceeding 2000 x 10(9)/L. Platelet counts remained elevated the first 4 years of life. A large deletion located at chromosome 17q11 was observed. The transient thrombocythemia may relate to a regulator of megakaryocytopoiesis located in the vicinity of the NF1 gene or to the excessive risk of chronic myelomonocytic leukemia in neurofibromatosis.

Although ET is a relatively rare disease and, in general, life expectancy of patients is similar to that of individuals without the disease, hemostatic complications are the major causes of mortality and morbidity in some patients. Hemostatic complications are most likely due to as yet poorly defined abnormalities in platelet-vessel wall interactions. Treatment modalities used in the past include cytoreductive therapy and antiplatelet therapy, although the basis of their use has been, until recently, only retrospective observations and not prospective, randomized clinical trials. The older therapeutic modalities, such as radiophosphorus (32P) and alkylating agents, have been largely abandoned because of their leukemogenic potential. The leukemogenic potential of hydroxyurea, presently the most widely used cytoreductive agent, remains uncertain. Interferon-alpha and anagrelide are promising newer drugs. However, because of the toxicity of these agents, there is a pressing need for prospective, controlled clinical trials to establish the indications for cytoreductive and antiplatelet therapy in different subsets of patients with ET. Ultimately, it can be anticipated that elucidation of the molecular basis of ET will permit specific targeting of therapy to the pathogenetic megakaryopoietic defect(s) in the disease.

This report suggests modest changes in the criteria used for the diagnosis of ET and allows tentative recommendations concerning therapy. As outlined in Table I, we believe that absent stainable marrow iron does not necessarily indicate iron deficiency in these patients and that the serum ferritin and RBC mean corpuscular volume should be incorporated in this assessment. Normal values speak strongly against iron-deficient erythropoiesis. A search for the bcr/abl gene rearrangement should be included with the marrow karyotype to exclude CML. Finally, cytogenetic data and morphologic study of the marrow should be used to be certain that a MDS should not be considered. It may be that measurements of serum thrombopoietin levels may be useful in the future. Nonetheless, in principle, ET remains a diagnosis of exclusion as we have originally suggested. For therapy, HU remains an excellent choice for the older patient at risk for thrombosis. Nonetheless, no myelosuppressive therapy remains a perfectly viable option, particularly for the young patient and the older with low thrombotic risk. The roles of anagrelide and alpha interferon in this setting have not been fully defined. Experience with both has still been relatively short. It would be ideal if prospective, randomized trials could be mounted to address these questions. We conclude with confidence that return to older approaches such as 32P and AA in patients who fail on HU is to be discouraged. The use of anagrelide or interferon alfa seems to be a much more appropriate approach. We have not investigated the role of antithrombotic agents such as aspirin in ET. In PV, the combination of aspirin, 300 mg three times daily, and dipyridamole, 75 mg three times daily, failed to reduce the rate of thrombosis and was associated with an increased rate of hemorrhage. It is rational to suggest that lower doses of aspirin (ie, < 325 mg daily) might be associated with less hemorrhage and, perhaps, a beneficial effect on thrombosis. This remains to be shown.

A patient with a history of essential thrombocytosis presented with diffuse skeletal pain and restricted motion of the left shoulder. Magnetic resonance imaging (MRI) of the left glenohumeral joint showed a soft tissue mass that displaced the rotator cuff. Biopsy of the mass revealed chloroma. MRI is the method that best characterizes this lesion.

The records of horses presented to the Veterinary Teaching Hospital of North Carolina State University College of Veterinary Medicine between January 1, 1989 and April 30, 1994 were evaluated to determine risk factors associated with thrombocytosis. Of the 2,346 horses for which a CBC was performed, 24 (1.0%) had a platelet count > 400,000/microL. Demographic, diagnostic, physical examination, and clinicopathologic variables from these cases were compared with a reference population consisting of 189 horses with a normal platelet count presenting during the same period. Infectious/ inflammatory disorders were observed more commonly in horses with high platelet counts than in horses with normal platelet counts. Initial independent evaluation of demographic variables revealed that horses more than 3 years of age, females, and geldings were less likely to have thrombocytosis than were younger horses or stallions. Independent analysis of clinicopathologic variables revealed that horses with thrombocytosis were more likely to have hyperfibrinogenemia, leukocytosis, hypoproteinemia, and anemia than were horses with normal platelet counts. Physical examination parameters associated with thrombocytosis included tachycardia and pyrexia. In the final multivariable model, the variables with the strongest association with thrombocytosis included leukocytosis, anemia, and hyperfibrinogenemia. Thrombocytosis rarely causes clinical problems in horses and is not likely to require specific antiplatelet therapy. The strong association of thrombocytosis with infectious/inflammatory disorders, however, should lead clinicians to suspect these types of conditions in horses with high platelet counts.

Basic Problem and Objective of Study: The diagnosis of polymyalgia rheumatica is made difficult by the absence of any pathognomonic findings. Erythrocyte sedimentation rate (ESR) and concentration of C-reactive protein are used as diagnostic criteria and to monitor the disease's course. It was the purpose of this study to evaluate prevalence of thrombocytosis and whether there is any correlation between thrombocytosis and ischaemic complications., Patients and Methods: In a retrospective study the data of 23 patients (14 women, 9 men; mean age 67.3 [48-84] years) with polymyalgia rheumatica were analysed: platelet counts, ESR and C-reactive protein had been measured at the time of diagnosis and 7, 14 and 21 days after start of glucocorticoid treatment. At the time of diagnosis 17 of 23 patients (74%) had a thrombocytosis (> 400,000/microliter), at a mean value of 511,000 (418,000-638,000)/microliter. The platelet count decreased more slowly than the inflammatory parameters. On average the platelet count returned to normal on the 14th day. Ischaemic complications developed in three patients (visual disturbances, blindness, cardiac arrhythmias, neurological deficits): all had a high platelet count (462,000-524,000/microliter)., Conclusions: Thrombocytosis can serve as an additional criterion in the diagnosis and follow-up of polymyalgia rheumatica. An association with ischaemic complications is especially likely in the elderly, in case of immobility and if there is evidence of giant-cell arteritis. Treatment with platelet aggregation inhibitors should be considered.

Clonogenic cultures support the proliferation of haemopoietic cells into colonies of differentiated progeny. Using these techniques it has been established that normal haemopoietic progenitors are dependent upon growth factors for their survival, proliferation and differentiation in vitro. However, progenitors from patients with polycythaemia vera (PV) generate erythroid colonies in cultures deprived of exogenous erythropoietin. These have been termed endogenous erythroid colonies (EEC). Recently, endogenous megakaryocytic colonies (EMC), those arising in assays without megakaryocyte growth factors, have been reported, particularly in patients with primary thrombocythaemia (PT). Many investigators have found an EEC positive culture to have 100% diagnostic specificity and sensitivity for PV. Similarly, EMC have been shown by some to be an unequivocal marker of PT. Accordingly, clonogenic assays for EEC and EMC have been advocated as diagnostic markers of PV and PT. However, the specificity of these assays is not universally attested to as there are some reports of EEC in patients with secondary polycythaemia and of EEC and EMC in normal subjects. Thus, for diagnostic use, EEC and EMC assays must be exhaustively validated for specificity using clinically appropriate controls. Furthermore, clonogenic culture techniques are not amenable to external quality assurance, are technically demanding and are unlikely to be available in most haematology laboratories. These considerations must be taken into account when assigning weighting to EEC and EMC assays as diagnostic criteria in myeloproliferative disorders.

Among the chronic myeloproliferative disorders essential thrombocythemia (ET) is known to be a distinct clinical entity in which an excessive number of morphologically and functionally abnormal platelets are produced. The clonal nature of the disease is well established. Based on a review of the literature the present authors propose the following novel criteria for the diagnosis of ET: A1. Platelet count in excess of 600 x 10(9)/L. A2. No increase in red-cell mass (RCM) in the presence of stainable iron in the bone marrow or failure of iron trial (RCM < 36 mL/kg in males and < 32 mL/kg in females; or RCM < 25% above mean normal predicted value*). A3. No Philadelphia chromosome. A4. Megakaryocytic hyperplasia (= increased megakaryocyte number and size) in histological sections of bone marrow and/or increased megakaryocytic ploidy (two-color flow cytometry); no collagen fibrosis. B1. Splenomegaly on isotopic scan or echogram. B2. Unstimulated growth of BFU-E and/or CFU-Meg present. B3. Normal ESR/fibrinogen. The diagnosis of ET is considered to be established if A1 + A2 + A3 + A4 or A1 + A2 + A3 + two B-criteria are fulfilled. (* Br J Haematol 1995; 89:748-756.)

The development of techniques permitting in vitro growth of human megakaryocytes progenitors and more recently identification of the proto oncogene c-mpl (Mpl-R) and its ligand (Mpl-L) have created new opportunities for studying pathophysiology of E.T. Plasma or serum of E.T. patients was unable to overestimulate MK colony formation by normal bone marrow cells. Significant increases in circulating CFU MK in E.T. patients have been repeatedly observed while in E.T. marrow, due to inappropriate sampling, colony number was not significantly different from normal. Spontaneous colony formation is observed in approximately 100% bone marrow and 85% blood from E.T. patients. Spontaneous colony formation persisted in plasma clot assay without added plasma or serum and in serum free agar cultures but only at a slightly lower rate than in plasma clot. Spontaneous colony formation in culture condition without plasma and serum were never observed with normal bone marrow and blood. Spontaneous MK growth was observed in a higher proportion of E.T. patients than erythroid colony formation but both phenomenon can occur in about 50% of the patients. CFU MK colony formation disappeared in serum free cultures using highly purified CD 34 cells. MK development is not completely independent of regular control. An hypersensitivity of E.T. MK progenitors to growth factors known to stimulate normal hematopoiesis (IL3.IL6, GM CSF, has been shown as well as a decreased sensitivity to negative regulators (TGF beta), has been suggested. The number of spontaneous MK colonies was not significantly decreased by added anti IL3, IL6 or anti GM CSF, antibodies in culture medium. Pre incubation of blood non adherent mononuclear cells of E.T. patients with antisense oligonucleotides to c-mpl significantly decreased the cloning efficiency of spontaneous megakaryocyte growth as compared to the introduction of scrambled oligomers. Finally m RNA expression of the Mpl-L (TPO) was not formed in MK spontaneously grown in serum free liquid cultures after 12 days. These results suggest that human c-mpl proto oncogene may be implicated in the pathway of spontaneous megakaryocytopoiesis in MPD but an absence of autocrine-stimulation by TPO of spontaneous growth in MPD. Analysis of peripheral blood cell clonality was performed in 55 E.T. patients using either the DNA methylation pattern of the androgen receptor (AR) gene or mRNA transcripts of G6PD or IDS genes. 51 out of 55 patients were informative. Non random X inactivation was found on unfractioned blood in 73% as compared with 23% in normal females (skewed Lyonisation). In 12 patients monoclonality of hematopoiesis was definitely confirmed by recording polyclonality of the mononuclear fraction or of T lymphocytes. In 4 patients monoclonal hematopoiesis was limited to platelets, 7 patients remained polyclonal in whole blood and all cellular fractions studied. MK colony formation (provided that the serum free agar culture system is clearly standardised) and clonality studies on whole blood or granulocyte, T lymphocyte and platelet fractions may be proposed as positive criteria for diagnosis of E.T.

The pathogenesis of essential thrombocythemia as a clonal myeloproliferative disorder has been clearly established. However, there continues to be considerable controversy concerning the management of this disease, particularly because its natural history is consistent with a nearly normal life expectancy. Therapeutic decisions have been complicated by a reliance on largely anecdotal, retrospective experience in the medical literature and, until very recently, an absence of prospective, controlled clinical trials. A recent study of patients with essential thrombocythemia at high risk of thrombosis because of advanced age or previous history of thrombotic complications demonstrated that platelet cytoreduction with hydroxyurea is effective in reducing thrombotic complications. Other cytoreducing agents that have been used in this disease include alkylating agents, recombinant interferon alpha, and anagrelide. The use of antiplatelet therapy is also controversial, and is most highly effective in patients with digital or cerebrovascular ischemic problems.

The authors' impression is that the CBC provides much more information than is routinely used. When anemia is present, the CBC contains considerable information regarding its cause, which can assist in formulating a differential diagnosis and directing further evaluation. White blood cell and platelet count levels may similarly direct practitioners to consider or dismiss underlying conditions. This article assists the pediatrician in optimizing use of this familiar diagnostic tool.

Lately, myeloprolipherative disorders are frequently reported as causes of portal vein thrombosis, probably due to the early detection of latent cases of this condition. We report two patients with portal vein thrombosis that presented with abdominal pain, nausea, vomiting and clinical consequences of portal hypertension such as variceal hemorrhage, splenomegaly and ascites. Diagnosis was made by a CAT scan in one patient and doppler ultrasound in the other. Both patients had high platelet counts and an essential thrombocytosis in the bone marrow.

Purpose: The purpose of this study was to describe the clinical course of patients seen with large-vessel thrombosis in association with essential thrombocytosis (ET)., Methods: This study was a retrospective review of all patients treated for large-vessel thrombosis caused by ET during a 2-year period at University of Washington teaching hospitals., Results: Five patients presented with arterial (femoral-popliteal-tibial: aortic), portal (two cases), or systemic venous (inferior vena cava) thrombosis and required operation. Two were known to have ET; in three others ET was diagnosed after operation when platelet counts persistently in excess of 500,000/mm3 were noted. The diagnosis of ET was established in each case by ruling out causes of reactive thrombocytosis and (in the three new cases) by evidence for megakaryocyte hyperplasia on bone marrow biopsy. Platelet counts in all five patients were reduced to normal levels by cytoreductive therapy, and no further thrombotic episodes have occurred during 18 months (mean) of follow-up. During this 2-year period ET accounted for more large-vessel thrombotic complications in our institutions than all other more frequently described hypercoagulable states combined., Conclusions: ET is an underemphasized cause of large-vessel thrombosis.

Background: Ischemic stroke as a presenting sign of essential thrombocythemia has been infrequently reported. We describe six patients in whom cerebrovascular disease was the first manifestation of this myeloproliferative disease. A positive endogenous megakaryocyte and/or erythroid colony growth from blood was a diagnostic criterion of essential thrombocythemia in patients with platelets counts lower than 600 x 10(9)/L., Case Descriptions: These six patients represented 0.54% of all patients with first stroke, 42.8% of all hematologic disorders associated with stroke, and 12.5% of all patients with essential thrombocythemia diagnosed from 1986 to 1992 at our institution. Eleven acute cerebrovascular accidents (6 transient ischemic attacks, 5 definitive cerebral infarcts) were registered. Mean time from ischemic stroke to diagnosis of essential thrombocythemia was 4.5 months (range, 1 to 12 months). The mean platelet count was 597 x 10(9)/L (range, 414 to 760 x 10(9)/L). Four patients had platelets counts lower than 600 x 10(9)/L. All patients had circulating erythroid progenitors, megakaryocytic progenitors, or both., Conclusions: Ischemic stroke as a presenting manifestation of essential thrombocythemia is probably underrecognized. The diagnosis of thrombocythemia should not be excluded on the basis of platelet counts lower than 600 x 10(9)/L. The availability of in vitro culture of hematopoietic progenitors from peripheral blood makes it possible to diagnose early and atypical cases.

The relationships among thrombocytosis, abnormal platelet aggregation and altered hemostasis in primary thrombocythemia remain poorly understood. Consequently, the appropriate management of asymptomatic patients is controversial and needs to be individualized. For symptomatic patients, conventional therapy, usually hydroxyurea, is directed primarily at lowering the platelet count by suppression of megakaryocyte activity. Recombinant interferon alpha can selectively lower platelet counts and may offer a reasonable alternative. Recent experience with anagrelide is also most promising in both symptomatic and asymptomatic patients. Current thoughts on the pathogenesis and management guidelines are presented here.

Spontaneous colony formation from bone marrow megakaryocyte progenitors (BMsCFU-Mk) was studied in 24 patients with essential thrombocythaemia (ET), 20 patients with reactive thrombocytosis (RT), 20 patients with polycthaemia rubra vera with thrombocytosis (PRVtr), 16 patients with chronic myeloid leukaemia with thrombocytosis (CMLtr) and 18 normal control subjects (C). The culture medium which was used in the methylcellulose assay in vitro contained 30% of plasma from a single patient with hereditary haemochromatosis. Remarkable BMsCFU-Mk growth was recorded in all patients with ET but in none with RT or in C. BMs-CFU-Mk were present in 11/20 patients with PRVtr and 7/16 patients with CMLtr. Spontaneous bone marrow erythroid progenitors (BMsBFU-E) were also determined in these patients. BMsBFU-E were found in 21/24 patients with ET and none in the patients with RT and C. All patients with PRVtr and one patient with CMLtr showed BMsBFU-E. We conclude that our implementation of the in vitro methylcellulose assay allows the BMsCFU-Mk to be used as an unequivocal test for discrimination between ET and RT which has not been shown in previously published studies. In addition, we present evidence that in 10 patients BMsCFU-Mk and/or BMsBFU-E growth in the test persisted after long-lasting haematological remission.

Background: The most potent stimulator for the hepatic synthesis of C-reactive protein is the interleukin-6. Also interleukin-6 is endowed with thrombopoietic activity, and its seric levels increases in most of secondary thrombocytosis whereas they remain normal in chronic myeloproliferative diseases or primary thrombocytosis. The aims of the study were verify the ability of quantitation of serum C-reactive protein in the differential diagnosis of primary thrombocytosis., Methods: Serum samples from 89 patients with thrombocytosis (> 400 x 10(9)/1) and 54 normal controls were assayed for C-reactive protein. Patients with thrombocytosis were classified in primary thrombocytosis with 27 patients (chronic myeloproliferative disease with thrombocytosis) and secondary thrombocytosis (62 cases)., Results: The mean C-reactive protein serum levels observed in the 27 patients with primary thrombocytosis were 13 +/- 10 mg/l, superior to normal controls (7 +/- 5 mg/l; p < 0.01). In the secondary thrombocytosis group, C-reactive protein serum levels reached a mean value of 59 +/- 34 mg/l, clearly superior to control group and the primary thrombocytosis group (p < 0.0001). No patients in primary thrombocytosis group reached a C-reactive protein value > 40 mg/l, versus 65% of patients in secondary thrombocytosis group. A normal value occurred in 67% cases of primary thrombocytosis group, but also in 17% cases of secondary thrombocytosis group., Conclusions: Quantitation of C-reactive protein could thus prove useful in the differential diagnosis between primary and secondary thrombocytosis.

We report a case of venous thrombosis presented as ischemic intracranial expanding lesion localized in the parietal lobe of a young man with essential thrombocytosis. As surgical intervention became necessary we were able to investigate the morphological changes by histology and immunocytochemistry. The almost exclusive venous manifestation of thrombosis most probably initiated by elevated amounts of platelets suggests altered blood flow conditions as the predominant factor. Surgical interventions in such conditions are rare and might only proceed in space-occupying lesions with clinical symptoms. Treatment with inhibitors of platelet aggregation under strict control of the patient is the therapy of choice.

Reactive thrombocytosis following cardiopulmonary bypass surgery is generally considered to be a benign condition which is transient and does not require specific therapy. We describe three patients who developed stroke in association with reactive thrombocytosis in the late recovery period following cardiopulmonary bypass surgery. No evidence of embolic or cerebrovascular disease was detected in any patient. Analysis of a larger group of patients is required in order to determine whether reactive thrombocytosis may contribute to the pathogenesis of stroke in some patients following cardiopulmonary bypass surgery.

The authors report three newborns with subcutaneous fat necrosis, that appeared between the 4th and 21st day of life. The infants, full term of normal weight, presented severe perinatal hypoxia and needed primary resuscitation. Severity and duration of perinatal hypoxia were not related with the time of cutaneous lesion onset. Serum calcium levels were in the higher values of the neonatal normal range. Vitamin D levels were within the normal range and only one patient showed a transient elevation of PTH, suggesting a poor relevance of both these factors in determining serum calcium increase. All patients showed a marked increase of platelets number, before the onset of clinical manifestations. Thrombocytosis could play an important role in the pathogenesis of adipose tissue necrosis, causing lower blood perfusion with relative hypoxia and hypothermia.

Traditional diagnostic criteria for primary thrombocythaemia (PT) remain essentially negative, aiming to exclude other myeloproliferative disorders and causes of reactive thrombocytosis (RT). It would be useful to have positive markers. We have examined several parameters to see how well they discriminate between PT and RT. Three groups of patients were studied: new, untreated PT (17), treated PT (12) and RT (17). Data consisted of: ESR, plasma fibrinogen, factor VIIIC, von Willebrand factor antigen (vWF:Ag), PDW, platelet nucleotide ratio (ATP:ADP) serum erythropoietin (Epo), ristocetin cofactor (vWF:RiCoF), multimeric structure of vWF, interleukin-6, evidence of clinical ischaemia and erythroid colony formation. Erythroid colonies were assayed in a serum-free system with the addition of Epo, IL3 or alpha-IFN to produce a discriminant function (DF) successfully used in the diagnosis of primary polycythaemia in an earlier study. Acute phase reactants (ESR, fibrinogen, VIIIC, vWF:Ag) and IL6 were the best discriminants, while PDW and serum Epo were less so. ATP:ADP and clinical ischaemia were nondiscriminatory in this study. Reduction in vWF:RiCof and in high molecular weight multimers were clearly associated with PT. Endogenous erythroid colonies were nondiscriminatory, but half the PT group and only one patient in the RT group obtained a DF suggestive of myeloproliferative disorder. Judicious use of a battery of tests may provide support for diagnosis of PT in difficult cases.

Megakaryocyte and erythroid colony formation in vitro by progenitors from the bone marrow and/or blood was studied in 61 patients with essential thrombocythaemia (ET) and 22 patients with reactive thrombocytosis (RT) using the methyl cellulose assay. 47 (77%) of the patients with ET showed megakaryocyte and/or erythroid spontaneous colony formation while 14 (23%) patients did not have any kind of spontaneous colonies. Spontaneous megakaryocyte colony formation was seen in 42 (69%) of the patients and 36 (59%) ET patients showed spontaneous erythroid growth. 31 patients had both types of spontaneous colonies. 11 patients showed only spontaneous megakaryocyte colony formation, and five patients only spontaneous erythroid growth. None of the patients with RT or of the normal controls showed either type of spontaneous growth. Neither the presence of spontaneous megakaryocyte colony formation nor the number of spontaneous colonies correlated with the platelet count. Patients with spontaneous megakaryocyte growth had significantly more often thromboembolic or haemorrhagic problems than those without spontaneous colony formation. In conclusion, it was found that a great majority of patients with ET but none of those with RT grow spontaneous megakaryocyte and/or erythroid colonies. Spontaneous colony formation is strong evidence for a myeloproliferative disorder. The presence of spontaneous colony growth is associated with an increased risk of thromboembolic or haemorrhagic complications regardless of the platelet count, particularly among young patients.

Reactive thrombocytosis is an elevation of platelet count occurring in association with certain underlying diseases such as various infections, inflammatory, neoplastic and asplenic states. Essential thrombocythemia is a myeloproliferative syndrome affecting megakaryocytes, which leads to increased numbers of circulating platelets. This disorder is characterized by splenomegaly and a clinical course punctuated by hemorrhagic and/or thrombotic episodes.

Essential thrombocytosis (ET) is currently diagnosed by histopathologic assessment of the marrow after exclusion of a secondary cause or another myeloproliferative disorder. To evaluate the potential of more direct diagnostic methods, we compared the frequency and association of several abnormal features characteristic of neoplastic precursors in 32 patients presenting with platelet counts > 500 x 10(9)/l. Assays for erythropoietin (Ep)-independent erythroid progenitors were performed on all patients, determination of the cycling status of circulating progenitors on 27, and assessment of granulocyte clonality on 15. In most, but not all, patients deregulated progenitor turnover. Ep-independent progenitors and clonal granulocytes were concordant findings. The presence of polyclonal granulocytes and lack of evidence of abnormalities in Ep-dependence or progenitor cycling were also concordant findings in most, but not all patients. Thus, normal (i.e. polyclonal) granulocytes may be produced in occasional patients in spite of the presence of a neoplastic clone. Interestingly, one third of patients thought to have ET on the basis of blood and marrow histopathology showed no abnormalities previously associated with neoplastic progenitors. These findings suggest variability in dominance of the neoplastic clone in some ET patients and the potential utility of a multifaceted laboratory approach to investigate the underlying pathology in patients with thrombocytosis.

The mean platelet volume (MPV) was evaluated in 68 dogs with thrombocytopenia attributable to various causes. Platelet size was high or low in some dogs. The most clinically useful observation was that low MPV (microthrombocytosis) was a specific indicator of immune-mediated thrombocytopenia (IMT) in these thrombocytopenic dogs. All but one case of microthrombocytosis (MPV less than 5.4 fl) was found in dogs with IMT. Microthrombocytosis was detected in 17 of 31 dogs with IMT and appeared at the onset of the disease. Macrothrombocytosis (MPV greater than 9.4 fl) indicated active thrombopoiesis, but was not unique to any disease category. Macrothrombocytosis was detected in 18 of 31 dogs with IMT, 3 of 17 dogs with disseminated intravascular coagulation, and 3 of 9 dogs with primary bone-marrow disease.