Increased number of B-cells in the red pulp of the spleen in ITP

Platelets are targeted by autoantibodies and destroyed in the reticuloendothelial system in the spleen, liver and bone marrow in patients with immune thrombocytopenia (ITP). Other mechanisms such as destruction by cytotoxic T-cells and defective production of platelets in the bone marrow also exist. Splenectomy normalizes the platelet count in 70% of ITP patients, however, precious little is known about the spleen in this disease. Our aim was therefore to investigate the splenic morphology and especially the number and localization of splenic leukocytes in patients with ITP and controls and to evaluate factors predicting outcome of splenectomy. Spleen sections from 29 ITP patients and 11 individuals splenectomized due to trauma were analyzed by immunohistochemistry. All except one of the ITP patients had a normalized platelet count 12 months after splenectomy and the platelet count was inversely correlated with age. ITP patients had an increased number of B-cells in the red pulp. The number of white pulp B-cells and number of T-cells in both compartments was unchanged. In conclusion, B-cells are increased in the red pulp of the spleen and together with cytotoxic T-cells, helper T-cells and macrophages line the sinusoids enabling the immunological attack on platelets in ITP.     

Acute idiopathic thrombocytopenic purpura in children

Acute idiopathic thrombocytopenic purpura (ITP) characteristically follows a viral illness in preschool children. The exact role of viruses in the pathogenesis of this disorder remains uncertain, but the finding of markedly elevated levels of platelet-associated IgG serves to distinguish it from the chronic form of the disease and permits speculation on the mechanisms of platelet destruction. Although the spleen is important in both antibody production and platelet destruction, bone marrow synthesis of IgG has also been shown to be increased. The clinical course may be alarming, but mortality is low and prognosis excellent. Controversy has surrounded the role of steroids in the management of acute childhood ITP in retrospective studies. Controlled studies, however, indicate that thrombocytopenia is reversed sooner in treated patients. New assays for platelet-associated IgG offer new insights into this disorder and will allow delineation of acute and chronic disease at the time of diagnosis.     

The Platelet Destruction Site in Thrombocytopenic Purpuras

The site of sequestration of ⁵¹Cr-labelled platelets has been studied in 465 subjects, of whom 317 suffered from idiopathic thrombocytopenic purpura. The validity of the method was demonstrated in several ways: a given subject usually showed the same site of platelet sequestration when investigated more than once even after a long interval; there were characteristic and very different platelet sequestration curves in the thrombocytopenias due to bone marrow hypoplasia, hypersplenism or ITP; and there was a correlation between the preoperative in vivo results and the radioactivity found in the spleen after splenectomy.
In ITP the destruction of labelled platelets was more often splenic in children and in patients whose thrombocytopenia responded to steroid therapy. There was a perfect correlation between the site of platelet destruction and the platelet rise immediately after splenectomy. There was a good correlation between the site of platelet destruction and the long-term effectiveness of splenectomy.     

Evaluation of the immature platelet fraction in the diagnosis and prognosis of childhood immune thrombocytopenia

Rapid assessment of platelet production would distinguish between thrombocytopenia due to decreased platelet production or increased peripheral platelet destruction. We evaluated the value of immature platelet fraction (IPF) in differentiating immune thrombocytopenia (ITP) from thrombocytopenia secondary to bone marrow failure and its potential use as a prognostic marker. Forty-one young patients with ITP were compared with 14 patients with hematological malignancies under chemotherapy, representing a control group with thrombocytopenia due to bone marrow suppression and 30 age- and sex-matched healthy controls. Patients were studied stressing on bleeding manifestations, organomegaly/lymphadenopathy and therapy. Complete blood count including IPF was performed using Sysmex XE-2100. ITP patients were classified into two subgroups: acute ITP with spontaneous resolution within 3 months from diagnosis and chronic ITP that lasted ≥1 year from diagnosis. Median IPF was 11.8% in patients with ITP, 7% in those with hematological malignancy and 3% in the control group (p?<?0.001). ITP patients had significantly higher mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (P-LCR) and IPF compared with patients with malignancy or healthy controls, while plateletcrit (PCT) was significantly lower in ITP patients than other groups (p?<?0.001). IPF was increased in patients with chronic ITP compared with acute ITP group (p?<?0.001). Patients with active ITP had the highest IPF followed by those in partial remission, while ITP patients in remission had the lowest IPF. IPF was positively correlated to the number of lines of treatment used, MPV, PDW and P-LCR, while negatively correlated to platelet count and PCT among ITP patients (p?<?0.001). Multiple regression analysis showed that platelet count and P-LCR were independently related to IPF. ROC curve analysis revealed that the cut-off value of IPF at 9.4% could be diagnostic for ITP patients with a sensitivity of 88% and a specificity of 85.7%. We suggest that IPF may be a rapid and inexpensive automated marker for etiology of thrombocytopenia and can be integrated as a standard parameter to evaluate the thrombopoietic state of the bone marrow. It may be considered as a potential prognostic marker for the development of chronic ITP.     

血小板生成素在慢性乙型肝炎血小板减少症中的作用

目的：探讨血小板生成素在慢性乙型肝炎血小板减少症患者中的作用。方法：对76例慢性乙型肝炎血小板减少症患者进行血清血小板生成素水平、凝血酶原活动度、骨髓巨核细胞计数检查。结果：血小板生成素水平与凝血酶原活动度、骨髓巨核细胞计数、外周血小板计数相关（r分别为0．423、0.396、0．297，P〈0．05）；76例患者标本中有22例骨髓巨核细胞计数〈7（个／4．5cm^2），占20％；巨核细胞成熟障碍29例，占38％。结论：血小板生成素在慢性乙型肝炎血小板减少症的发病机制中起一定作用。     

Isolated thrombocytopenia after allogeneic bone marrow transplantation: existence of transient and chronic thrombocytopenic syndromes

Isolated thrombocytopenia after bone marrow transplantation was investigated in 65 fully engrafted patients surviving at least 60 days posttransplant. Twenty-four patients (37%) developed this complication, which occurred most frequently in patients receiving pretransplant preparation with total body irradiation or busulfan. Two distinct thrombocytopenic syndromes were identified: (1) transient thrombocytopenia (nine patients), in which a normal platelet count (greater than 100,000/microL) was initially established by day +40 but then diminished to less than 10,000 to 45,000/microL on day +40 to +70, with subsequent resolution of the thrombocytopenia by day +90; (2) chronic thrombocytopenia (15 patients), in which a platelet count greater than 100,000/microL was not achieved at any time during the first four months posttransplant, despite the simultaneous presence of normal granulocyte and reticulocyte counts. Although the transient syndrome did not adversely affect prognosis, the chronic syndrome carried a high mortality (21% actuarial survival at 1,000 days posttransplant compared with 67% survival for all patients, P less than .01) and had a high association with both severe (grades 3 to 4) acute graft-versus-host disease (GVHD) and chronic GVHD. In three of nine patients with transient thrombocytopenia, a temporal association with trimethoprim-sulfamethoxazole administration was observed, whereas in all other patients, no drug association could be found. Bone marrow biopsies in those patients with drug-associated thrombocytopenia showed decreased numbers of megakaryocytes, whereas biopsies in the remainder of the transiently thrombocytopenic patients demonstrated adequate numbers of platelet precursors, suggesting peripheral platelet destruction or ineffective thrombopoiesis. Biopsies in the chronic thrombocytopenic patients included those with and without adequate numbers of platelet precursors, although the association with chronic GVHD was strongest in patients demonstrating normal numbers of megakaryocytes. We conclude that isolated thrombocytopenia represents a significant complication of bone marrow transplantation, particularly in patients receiving hematopoietic ablative preparatory regimens, and that it is the chronic, not the transient, thrombocytopenic syndrome that is associated with an adverse patient prognosis.     

Kinetics and distribution in vivo of 111In-labelled autologous platelets in idiopathic thrombocytopenic purpura

The kinetics of autologous 111In-labelled platelets were studied in 26 patients with ITP. The platelet mean life time (MLT) was considerably shortened, the platelet in vivo recovery slightly lowered and the platelet turnover normal. Comparative studies of the kinetics of simultaneously injected 111In- and 51Cr-labelled platelets in 10 patients showed the MLT and turnover of 51Cr-platelets to be shorter and higher, respectively, than those of 111In-platelets, suggesting that 51Cr-labelling in ITP may underestimate platelet MLT and overestimate platelet turnover. Our results confirm that accelerated platelet destruction is an important pathogenetic factor in ITP, and that the platelet concentration may be influenced by increased splenic platelet pooling and by inability of the bone marrow to respond adequately to the low platelet count. Our scintigraphic studies showed that the spleen played an important role for platelet destruction in most patients, with the liver contributing in some patients.     

Platelet-associated IgG and IgM in myelofibrosis

Elevated levels of platelet-associated IgG and/or IgM were found in 15 of 18 patients with myelofibrosis (83 %). All but 5 patients with elevated PAIg had active disease. The amounts of PAIg were not correlated to either S-Ig, platelet count or spleen size. Levels of PAIgG well above the normal range were especially found in patients with short duration of disease and/or a transitional myeloproliferative state. It is debated whether immune-mediated platelet dysfunction may be of importance for the development of bone marrow fibrosis, mediated by the release of platelet-derived growth factors in the bone marrow. Elevated PAIg may also contribute to abnormal haemostasis and thrombocytopenia in myelofibrosis.     

Thrombocytopenia in chronic liver disease

Thrombocytopenia is a common haematological disorder in patients with chronic liver disease. It is multifactorial and severity of liver disease is the most influential factor. As a result of the increased risk of bleeding, thrombocytopenia may impact upon medical procedures, such as surgery or liver biopsy. The pathophysiology of thrombocytopenia in chronic liver disease has long been associated with the hypothesis of hypersplenism, where portal hypertension causes pooling and sequestration of all corpuscular elements of the blood, predominantly thrombocytes, in the enlarged and congested spleen. Other mechanisms of importance include bone marrow suppression by toxic substances, such as alcohol or viral infection, and immunological removal of platelets from the circulation. However, insufficient platelet recovery after relief of portal hypertension by shunt procedures or minor and transient recovery after splenic artery embolization have caused many to question the importance and relative contribution of this mechanism to thrombocytopenia. The discovery of the cytokine thrombopoietin has led to the elucidation of a central mechanism. Thrombopoietin is predominantly produced by the liver and is reduced when liver cell mass is severely damaged. This leads to reduced thrombopoiesis in the bone marrow and consequently to thrombocytopenia in the peripheral blood of patients with advanced‐stage liver disease. Restoration of adequate thrombopoietin production post‐liver transplantation leads to prompt restoration of platelet production. A number of new treatments that substitute thrombopoietin activity are available or in development.     

Graft-v-host disease is associated with autoimmune-like thrombocytopenia [see comments]

Persistent thrombocytopenia after allogeneic marrow transplantation is associated with poor patient survival. To identify the mechanisms of the thrombocytopenia, we studied platelet and fibrinogen kinetics and antiplatelet antibodies in 20 patients between 60 and 649 days (median 90) after transplantation. Seventeen patients had isolated thrombocytopenia (less than 100 X 10(9) platelets/L): the marrow cellularity was normal in five patients and slightly reduced in 12, and there was no discrepancy between thrombopoiesis and myeloerythropoiesis. Three patients had pancytopenia following marrow graft rejection (two) and relapse of leukemia (one). Only three patients had evidence of increased platelet production, indicating that in most cases there is a poor marrow response to thrombocytopenia early after marrow grafting. There was no correlation between platelet count and splenic pooling, suggesting that hypersplenism was an unlikely mechanism of the thrombocytopenia. Although there was a direct relationship between platelet count and platelet survival, the reduction in platelet survival was greater than what could be explained by the fixed platelet removal found in thrombocytopenic patients; this suggests increased platelet destruction. Seven patients had intercurrent infections that reduced both platelet and fibrinogen survivals. In addition, platelet antibodies bound to autologous or marrow donor platelets were present in five of the 12 patients studied. Patients with antiplatelet antibodies had lower platelet counts (30 +/- 10 X 10(9)/L v. 49.1 +/- 28.7 X 10(9)/L, P less than 0.05) and platelet survivals (1.32 +/- 0.92 days v. 3.58 +/- 2.02 days, P less than 0.05) than patients without antiplatelet antibodies. Furthermore, platelet- bound autoantibodies were present in five of six patients with grade II- IV acute or chronic graft-versus-host disease (GVHD), but were not present in six patients free of GVHD (P less than 0.01). We conclude that persistent thrombocytopenia after marrow transplantation is most often secondary to increased platelet destruction mediated by multiple mechanisms and that platelet autoantibodies are found in patients with acute or chronic GVHD.     

Different patterns of platelet turnover in chronic idiopathic thrombocytopenic purpura

Platelet turnover, platelet production, platelet mean life span (MLS), platelet count, mean platelet volume (MPV) and platelet-associated antibodies have been examined in 26 patients with chronic idiopathic thrombocytopenic purpura (ITP) and in 1 patient with hypomegakaryocytic thrombocytopenia (HT). 15 ITP patients had normal or increased platelet turnover and platelet production, while 11 had subnormal values despite shortened MLS, while the patient with HT had normal MLS. The differences between the two groups with high and low platelet turnover were statistically significant. No correlation was found between kinetics parameters and bone marrow pattern in a total of 19 patients examined. These data suggest that in some cases of chronic ITP, the pathogenesis of thrombocytopenia can be due not only to the peripheral destruction of platelets, but also to a deficient platelet production by megakaryocytes. Since the number of megakaryocytes in bone marrow slides is not decreased in the low turnover compared with the high turnover group, it is possible that an impaired pattern of megakaryocyte maturation be the cause of the low platelet production in these patients, unlike in the HT patient where megakaryocytes are almost absent.     

Kinetics of 111In-labelled platelets in healthy subjects

25 healthy subjects underwent platelet kinetic and scintigraphic studies following injection of 111In-labelled platelets. Using the multiple hit model, platelet mean lifetime averaged 185.3 hours (range 141.2-225.6), and platelet in vivo recovery averaged 56% (range 42-89). The platelet disappearance pattern was almost linear. However, in comparison with simultaneously injected 51Cr-labelled platelets (7 subjects studied), the 111In-platelet survival curves were slightly more curved. Our results indicate that this may be ascribed to a slight degree of elution of 111In from the circulating platelets. The plateau or even slight increase in circulating activity following the initial steep decline in activity appears mainly to reflect reversible sequestration of platelets in the spleen and maybe in the liver. Using a semiquantitative scintigraphic approach, we estimated 45%, 25% and 30% platelet destruction to occur in the spleen, liver and bone marrow, respectively. Our results indicate that the discrepancy between the course of circulating platelet-bound activity and of chest wall activity reflects platelet destruction in the bone marrow.     

病毒性肝炎血小板减少症影响因素的研究

目的探讨病毒性肝炎血小板减少症的发病机制.方法 84例病毒性肝炎患者和20名健康志愿者分为3组,A组(48例病毒性肝炎并血小板减少症患者)、B组(36例病毒性肝炎血小板正常患者)和C组(20名健康志愿者),分别采用酶联免疫吸附法、流式细胞术、腹部彩色B超检测3组血清血小板生成素(TPO)水平、血小板相关免疫球蛋白(PAIg)及其类别PAIgG、PAIgA、PAIgM水平、脾脏大小,采用骨髓穿刺术对其中74例行骨髓细胞学检查.结果血清TPO水平A组低于C组(P<0.01)和B组(P<0.05),严重肝病血清TPO水平与血小板数相关(r=0.374,P<00.01).PAIg、PAIgG水平A组明显高于B组(P<0.001)和C组(P<0.01),血小板数与PAIg水平呈负相关(r=0.446,P<0.01),血小板数与PAIgG水平亦呈负相关(r=-0.462,P<0.01).脾脏肿大发生率A组(77.1%)明显高于B组(47.2%,P<0.01),C组无脾脏肿大发生,血小板数与脾脏大小呈负相关(r=-0.5 81,P<0.01).74例骨髓象显示A组有4例呈骨髓抑制象改变,B组和C组无一例有上述改变.结论严重肝功能受损时血清TPO水平下降,与血小板数减少直接相关.PAIg介导的自身免疫机制在病毒性肝炎血小板减少症中可能起重要作用.脾脏肿大是引起病毒性肝炎血小板减少的因素.初步发现慢性肝病有骨髓抑制现象,可能成为引起病毒性肝炎血小板减少的因素之一.     

Hepatic fibrosis plays a central role in the pathogenesis of thrombocytopenia in patients with chronic viral hepatitis

The pathogenesis of thrombocytopenia in chronic hepatitis is not well known. This study evaluated the relationship between liver injury, serum thrombopoietin, splenomegaly and thrombocytopenia in chronic viral hepatitis. Two hundred and nine patients were enrolled, 85 with splenomegaly and 124 without. Thrombocytopenia was present in 71% and 23% of patients with or without splenomegaly respectively. In subjects with low platelet count, those with splenomegaly showed significantly lower platelet numbers than those without splenomegaly. The spleen size correlated with portal hypertension. An inverse correlation between spleen size and platelet count was observed (r = -0.54; P < 0.0001). In patients without splenomegaly, thrombocytopenia was associated with the grade of fibrosis; platelet counts were the highest in patients with fibrosis 0-2, lower in those with grade 3 (P < 0.008) and lowest in those with grade 4 (P < 0.05). These findings were independent of demographic and biochemical characteristics, hepatic necroinflammatory activity, portal hypertension and splenomegaly. Patients with normal platelet counts showed higher thrombopoietin levels than those with low platelet counts (P < 0.0001). An inverse correlation between thrombopoietin levels and fibrosis grade was observed (r = - 0.50; P < 0.0001). Median thrombopoietin levels were 58 and 27 pg/ml for fibrosis grade 0-1 and grade 4 respectively (P < 0.001). These data indicate that advanced hepatic fibrosis, causing an altered production of thrombopoietin and portal hypertension, plays the central role in the pathogenesis of thrombocytopenia in chronic viral hepatitis.     

Clinical use of beta-thromboglobulin levels in diagnosing and treating consumptive and immune thrombocytopenia

Plasma beta-thromboglobulin (beta-TG), a platelet-specific protein, is a marker of intravascular platelet degranulation. We measured plasma beta-thromboglobulin by radioimmunoassay in 13 patients with thrombocytopenia of various etiologies to determine whether or not the test is clinically useful in the differential diagnosis of thrombocytopenia. Four patients with intravascular platelet consumption (three with thrombotic thrombocytopenic purpura and one with vasculitis) had significantly higher plasma beta-thromboglobulin levels than four patients with extravascular platelet destruction due to idiopathic thrombocytopenic purpura. Five patients with thrombocytopenia and decreased numbers of megakaryocytes in the bone marrow also had beta-thromboglobulin levels that were not elevated. Two patients with thrombotic thrombocytopenic purpura achieved clinical remission associated with a decrease in beta-TG level to the normal range. Plasma beta-thromboglobulin determination can be useful in determining the mechanism of thrombocytopenia when bone marrow examination demonstrates adequate megakaryocyte numbers.     

Megakaryocytopoiesis in Experimentally Induced Immune Thrombocytopenia

The hypothesis that in immune thrombocytopenia, platelet antibody maynot only cause destruction of the circulating platelets but also depress plateletproduction by injuring the megakaryocytes of the bone marrow, was testedexperimentally.

Sustained thrombocytopenia was produced in rats by titrated injections ofa potent heteroimmune antiplatelet serum and megakaryocytopoiesis wasthen studied by the use of tritiated thymidine and bone marrow autoradiography. Rats in which the platelet count was maintained at a lower thannormal level by repeated thrombocytophereses, and other rats injected withplatelet antiserum previously absorbed with rat platelets, served as controls.

Profoundly altered patterns of megakaryocytopoiesis were found in the ratsin which thrombocytopenia was produced by the antiplatelet serum. The dataindicated a severely impaired and depressed megakaryocyte maturation and,possibly, destruction of some of the megakaryocytes during their maturationprocess. In the rats in which the platelet level was maintained low by repeatedthrombocytophereses, the pattern of megakaryocytopoiesis indicated accelerated maturation and there was also an increased megakaryocyte mass. Nodifference from normal was found in the rats receiving the platelet-adsorbed antiserum. It was concluded that the platelet antibody produced aninjurious effect on the megakaryocytes in the bone marrow, thereby depressing platelet production, and that the immune thrombocytopenia was theresult of both increased platelet destruction and defective platelet production.

Submitted on November 22, 1968 Accepted on October 3, 1969     

Thrombopoietin concentrations in peripheral blood correlated with platelet numbers in two patients with thrombocytopenia by chronic graft-versus-host disease

Thrombocytopenia is well known to be one of the clinical manifestations of chronic graft-versus-host disease (cGVHD). However, there exist cases in which the cause of thrombocytopenia has been unexplained. Recently, thrombopoietin (TPO) from bone marrow (BM) stromal cells and transforming growth factor (TGF)-beta from platelets and megakaryocytes have been identified as strong positive and negative regulators of megakaryopoiesis in vivo. We hypothesized that the decreased TPO production from BM could be one of the causes of thrombocytopenia in the patients with cGVHD. In the present study, therefore, TPO and TGF-beta concentrations in peripheral blood (PB) and BM were measured serially in two patients with acute leukemia who had received fully matched stem cell transplantation from relatives and subsequently developed extensive cGVHD with thrombocytopenia. The results showed that platelet numbers correlated well with the TPO concentrations, which were consistently higher in BM than in PB. The difference in TPO concentrations between BM and PB was decreased when the platelet levels were low, indicating that the amount of TPO production from BM decreased throughout the duration of thrombocytopenia. TGF-beta concentrations were normal during all periods in which measurements were carried out. Thus, our results suggest that one mechanism of thrombocytopenia in patients with cGVHD is low TPO production by BM cells.     

Peripheral destruction of platelets in chronic lymphocytic leukemia: Recognition,prognosis and therapeutic implicatio

In patients with chronic lymphocytic leukemia and depressed platelet counts, it is important to discriminate between the thrombocytopenia due to bone marrow replacement with abnormal lymphocytes and that caused by increased peripheral destruction of platelets. The former is due to progressive chronic lymphocytic leukemia and, as a Rai Stage IV, carries a poor prognosis. The latter, as illustrated in four patients seen at the National Cancer Institute, may be remediable by either splenectomy alone or splenectomy followed by immunosuppressive and antitumor therapy. In all four patients, survival was substantially longer than for patients whose condition was classified as Rai Stage IV. The importance of identifying the subgroup of patients with chronic lymphocytic leukemia with reversible thrombocytopenia is emphasized by these examples.     

Dasatinib enhances megakaryocyte differentiation but inhibits platelet formation

Dasatinib is a novel, potent, ATP-competitive inhibitor of Bcr-Abl, cKIT, and Src family kinases that exhibits efficacy in patients with imatinib-resistant chronic myelogenous leukemia. Dasatinib treatment is associated with mild thrombocytopenia and an increased risk of bleeding, but its biological effect on megakaryocytopoiesis and platelet production is unknown. In this study, we show that dasatinib causes mild thrombocytopenia in mice without altering platelet half-life, suggesting that it inhibits platelet formation. Conversely, the number of megakaryocytes (MKs) in the bone marrow of dasatinib-treated mice was increased and the ploidy of MKs derived from bone marrow progenitor cells in vitro was elevated in the presence of dasatinib. Furthermore, a significant delay in platelet recovery after immune-induced thrombocytopenia was observed in dasatinib-treated mice even though the number of MKs in the bone marrow was increased relative to controls at all time points. Interestingly, the migration of MKs toward a gradient of stromal cell-derived factor 1α (SDF1α) and the formation of proplatelets in vitro were abolished by dasatinib. We propose that dasatinib causes thrombocytopenia as a consequence of ineffective thrombopoiesis, promoting MK differentiation but also impairing MK migration and proplatelet formation.     

The extrahepatic uptake of198Au as an index of portal hypertension

A study was undertaken to determine if extrahepatic recticuloendothelial uptake of¹⁹⁸Au during hepatic scanning could be used as a measure of the portal venous pressure in patients with chronic diffuse liver disease. Twenty patients were studied by history, physical examination, liver function studies, liver biopsy, esophagoscopy,¹⁹⁸Au hepatic scan and wedged hepatic vein pressure measurements. Patients were separated into 2 groups: Group A—patients with neither spleen or lumbar vertebral bone marrow uptake of¹⁹⁸Au; Group B—patients with significant spleen and/or vertebral bone marrow uptake of isotope. Each of the 6 patients in Group A had a hepatic wedge pressure under 18 mmHg, and none had varices on esophagoscopy. All 14 patients in Group B had hepatic wedge pressures of 18 mmHg or more. Only 8 Group B patients had varices on esophagoscopy. These data suggest that the¹⁹⁸Au hepatic scan is a safe and valuable procedure for estimating the degree of portal venous hypertension in patients with diffuse chronic liver disease. In these 20 patients, if spleen or vertebral bone marrow uptake of isotope was present, the portal venous pressure was 18 mmHg or greater. If spleen and/or bone marrow uptake was lacking, then the portal venous pressure was below 18 mmHg.