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PubMed1979

Chromosome changes in a patient achieving complete remission in the acute phase of chronic myelogenous leukemia.

A patient with chronic myelogenous leukemia (CML) had a Philadelphia chromosome (Ph') [t(9q+;22q-)] in all cells and trisomy C in 13% of cells (later determined to be trisomy 8) at the time of diagnosis. After 21 months of intermittent treatment with busulfan, the acute phase developed with the appearance of an additional abnormality (trisomy ? 19). During a complete remission and reconversion to the chronic phase, trisomies 8 and ? 19 DISAPPEARed, although the Ph' remained. Following a period of marked thrombocytosis, a second relapse occurred with the reappearance of both marker chromosomes.

Adult↗
PubMed1984

The relation of megakaryocyte ploidy to platelet volume.

To determine how alterations of megakaryocyte proliferation will affect platelet production, we measured mean platelet volume (MPV), platelet volume heterogeneity, platelet count, and mean megakaryocyte ploidy in 42 patients. In normal subjects, mean platelet volume and megakaryocyte ploidy were related inversely but nonlinearly to platelet count, whereas mean platelet volume and platelet volume heterogeneity were related directly. In patients with immune thrombocytopenic purpura (low platelet count, MPV above normal, and increased megakaryocyte ploidy), and in those with reactive thrombocytosis (high platelet count, low MPV and megakaryocyte ploidy), the relation of MPV to megakaryocyte ploidy, platelet volume heterogeneity, and platelet count resembled or extended the relations found in normal subjects. By contrast, in patients with aplastic anemia or megaloblastic anemia, or in patients who were undergoing chemotherapy for leukemia, heterogeneity was increased abnormally at any MPV, and both MPV and megakaryocyte ploidy were substantially lower, at any platelet volume, than in normals or the above other groups. The most common ploidy class was 8N in all patients, and the mean megakaryocyte ploidy correlated directly and linearly with mean platelet volume. The data show that bone marrow with megakaryocytes of higher ploidy produces platelets that are both larger and more heterogeneous.

Blood Platelets↗
PubMed1987

Essential thrombocythemia associated with recurrent abortions and fetal growth retardation.

Essential thrombocythemia (ET) is one of the myeloproliferative disorders characterized by an elevated platelet count, usually greater than 1,000 X 10(9)/L. It may be associated with either hemorrhagic or thrombotic tendencies. Although it usually affects older people, we have recently encountered two young women with ET who had a total of six spontaneous abortions before the end of the first trimester. During her most recent pregnancy, one of the patients underwent plateletpheresis on four separate occasions before the 12th week. She reached 34 weeks but demonstrated evidence of fetal growth retardation and pre-eclampsia. At delivery there were scattered villus infarcts in the placenta. Based on this patient and previous reports in the literature, we postulate that the spontaneous abortions, fetal growth retardation, and pre-eclampsia may be related to the thrombocytosis and suggest that the use of antiplatelet agents throughout pregnancy should be seriously considered in such cases.

Abortion, Habitual↗
PubMed1988

Acute leukemia following treatment of polycythemia vera and essential thrombocythemia with uracil mustard.

Transformation to acute leukemia (AL) is known to occur in polycythemia vera (PV) and essential thrombocythemia (ET). Myelosuppressive therapy with agents such as 32P and alkylating agents increase this risk in both disorders. The alkylating agent, uracil mustard (UM), which is an effective agent for controlling thrombocytosis, has not been reported to be leukemogenic. We have treated 29 patients with UM (9 treated continuously and 20 treated intermittently): II with PV, 16 with ET, and 2 with myelofibrosis (MF). Three patients developed AL, two after continuous therapy. These two patients with PV had received the fourth highest and highest total dose of UM, and their duration of treatment was the third and fourth longest among the nine patients treated continuously, respectively. One out of 20 patients treated intermittently with UM developed AL. This patient (3) with ET had received the highest total dose of UM, and her duration of treatment was the longest among the 20 patients treated intermittently.

Acute Disease↗
PubMed1988

An antibody to platelet membrane antigen associated with thrombotic events in essential thrombocythemia.

A 71-year-old man with essential thrombocythemia presented with acute onset of thrombosis in his fingers. The platelet count at presentation was 752 x 10(9)/liter, and his PTT was within the normal range. Platelet aggregation was normal in response to ADP, decreased to epinephrine, and absent to collagen, with the patient receiving 1.2 g aspirin/day. Plasma vWF:Ag was 158 U/dl, VIII:C was 150 U/dl, and the vWF:Ag multimer pattern was normal. HLA antibodies were not detected in his serum, and the platelet-associated IgG was normal at 3.9 fg/platelet. Incubation of normal, unactivated platelets with the patient's plasma did not result in agglutination of the platelets. However, a serum antibody reacting against a platelet antigen with an apparent molecular weight of 45,000 could be demonstrated by Western blotting. This antibody also reacted with endothelial cells. The reactive pattern was similar to that of commercially obtained actin; the serum antibody could be removed by preincubation with actin. Platelet-plasmapheresis was carried out daily for 10 days, after which the serum still reacted weakly with the platelet antigen. By day 20, the band could still be identified on the electroblot, but 2 weeks later no band could be seen. Similar assay of sera from six other patients with myeloproliferative disorders and comparable thrombocytosis but without thrombotic manifestations did not show any such reactions. The data suggest a correlation between the presence of an antibody possibly directed against platelet and/or endothelial cell actin and the vascular events in this patient with essential thrombocythemia.

Aged↗
PubMed1990

The size and number of bone marrow megakaryocytes in malignant lymphoma and their relationship to abnormalities in platelet count.

Platelet counts were measured routinely in 718 volunteer blood donors and 124 patients with malignant lymphoma. When considered by gender, the mean platelet counts of the patients with malignant lymphoma were significantly increased when compared to controls (P less than 0.01). In addition, 9% of males and 4% of females with lymphoma exhibited a thrombocytosis, in which their platelet counts exceeded the upper limit of the normal platelet count for control subjects (defined as 2 SDs in excess of the mean value). Megakaryocyte whole size, cytoplasmic and nuclear sizes, and megakaryocyte numbers were also quantified in bone marrow obtained from the iliac crest of 5 hematologically normal subjects and 26 patients with malignant lymphoma. Mean megakaryocyte sizes were significantly greater in subjects with lymphoma, when compared to control values (P less than 0.05). No significant differences in megakaryocyte numbers in bone marrow were observed between the two groups. For subjects with malignant lymphoma, platelet count was found to be significantly positively correlated with megakaryocyte size. The results of this study suggest that the elevated platelet count associated with malignant lymphoma is mediated by an increase in the size of the megakaryocytes in the bone marrow.

Adolescent↗
PubMed1994

Low-dose ARA-C consistently induces hematologic responses in the clinical 5q- syndrome.

Five patients with the classical clinical syndrome associated with a deletion of the long arm of chromosome 5, i.e., anemia, macrocytosis, and thrombocytosis, or a normal platelet count, were treated successfully with subcutaneous low-dose cytosine arabinoside (LDARA-C). Prior therapy with other drugs had failed in four of the five patients. A total of nine complete and one partial hematologic responses were induced in five patients. Duration of the first hematologic response ranged from 3 to 30+ months. Two patients (cases 3 and 4) continue in their first hematologic response at 29 and 30 months. Upon relapse, up to three responses could be reinduced in two patients. Duration of the subsequent hematologic responses in case 1 was 16, 8, and 10 months and case 2 achieved two responses of 15 and 18+ months duration. LDARA-C therapy was associated with mild to severe neutropenia and moderate to severe thrombocytopenia. Thus, subcutaneous LDARA-C is highly effective in the treatment of patients with myelodysplasia associated with deletion of the long-arm of chromosome 5 (5q-).

Aged↗
PubMed2005

The natural history of severe anemia in cartilage-hair hypoplasia.

Anemia is seen in over 80% of patients with cartilage-hair hypoplasia (CHH). While this is usually mild and self-limited, some patients demonstrate a severe, persistent anemia resembling that seen in Diamond-Blackfan anemia (DBA). This paper examines the natural history of 12 patients with CHH and severe anemia. Phenotypic features and mutation data (where available) were reviewed, but no significant differences were found that predicted severe anemia. Severe anemia is estimated to occur in approximately 6% of CHH patients and is permanent in more than half of these patients. Thrombocytosis, though not previously reported in CHH, was noted in five patients, similar to that seen in DBA. The role of possible gene-gene and gene-environment interactions is discussed.

Abnormalities, Multiple↗
PubMed1979

Cerebral and retinal vascular complications of inflammatory bowel disease.

Recurrent retinal branch artery occlusions, carotid thromboembolism, cerebral venous thrombosis, transient brainstem ischemia, and massive brainstem and cerebral infarction complicated the course of inflammatory bowel disease in 5 patients. Three patients had ulcerative colitis and 2 had regional enteritis. The usual risk factors for stroke were absent. Neuropathological examination in 1 patient showed in situ thrombosis of small cerebral and brainstem arteries and veins. Coagulation studies showed thrombocytosis, short partial thromboplastin times, and elevation of fibrinogen and Factor VIII levels. Platelet counts and coagulation factors returned toward normal after control of intestinal inflammation in each of the 4 surviving patients. Inflammatory bowel disease can be accompanied by a hypercoagulable state that predisposes to stroke.

Adult↗
PubMed1989

Solitary plasmacytoma of the skull revealed by a mononeuritis multiplex associated with immune complex vasculitis.

We describe a patient with solitary plasmacytoma of the skull, in whom mononeuritis multiplex was the presenting manifestation. Some features of the POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal [M] protein, skin changes), including thrombocytosis, were found. Muscle and nerve biopsies disclosed a small vessel hypersensitivity-type vasculitis and complement-fixing immune complex deposits in vessel walls. Removal of the plasmacytoma resulted in clinical improvement and clearance of the vasculitis and immune complex deposits.

Adult↗
PubMedDate not supplied

Carcinomatous polyarthritis. The presenting symptom of an ovarian tumor and association with a platelet activating factor.

A 59-year-old white female presented with an acute polyarthritis, fever, and mental confusion. Accompanying blood changes included positive tests for rheumatoid factor and antinuclear factor, anemia, leukocytosis, thrombocytosis, and a circulating factor that stimulated serotonin release from normal platelets. Exploratory laporatomy for a mobile pelvic mass revealed an adenocarcinoma of the left ovary which was completely resected. Shortly thereafter the patient's acute symptoms subsided. After 2 years of follow-up the patient has remained free of symptoms and the serologic changes have reverted to normal.

Adenocarcinoma↗
PubMed1983

The role of hypertension in the vascular disease and myocardial infarcts associated with murine systemic lupus erythematosus.

The several kinds of mice that spontaneously develop acute systemic lupus erythematosus (SLE)--BXSB males, MRL/l males and females, and (NZB X W)F1 females--have a 15-20% incidence of degenerative vascular disease (DVD) and myocardial infarcts (MI) in which the affected coronaries contain deposits of immunoreactants, presumably in the form of immune complexes. Among the F1 hybrid crosses of SLE mice, only the (NZW X BXSB)F1, (W X B)F1 male has a significantly higher incidence of DVD/MI (80%). Search for possible causes of this high incidence of myocardial infarcts revealed several unique features of this mouse: hypertension, thrombocytosis, and early onset of circulating immune complexes and glomerulonephritis. Our attempts to prevent this DVD/MI focused on: reduction of hypertension, prevention of thrombosis, and immunosuppression. Immunosuppression by Cytoxan resulted in almost complete prevention of both the SLE disease and DVD/MI. Administration of bretylium, an antihypertensive and anti-arrhythmic agent, resulted in reduction of blood pressure and the severities of glomerulonephritis, DVD, and MI; it also slightly reduced the levels of circulating immune complexes and leukocytosis. Of the 4 antithrombotic agents used, only aspirin showed some reduction in the incidence of DVD/MI and delay of glomerulonephritis-associated mortality.

Animals↗
PubMed1990

Intravenous gamma globulin therapy in systemic juvenile rheumatoid arthritis.

Intravenous (IV) gamma globulin has been successfully used as replacement therapy for antibody-deficient patients and, more recently, in the treatment of autoimmune diseases such as idiopathic thrombocytopenic purpura, myasthenia gravis, and Kawasaki disease. In view of the successful treatment of these diseases, we initiated a pilot study of the effect of IV gamma globulin in systemic juvenile rheumatoid arthritis (JRA). Eight patients with active systemic JRA that was unresponsive to first-line agents, second-line agents, and/or corticosteroids received this therapy monthly for 6 months. Outcome measures included changes in articular and extraarticular features, steroid dosage, and laboratory parameters. Following IV gamma globulin therapy, there was significant improvement in arthritis and/or morning stiffness in 5 of 8 patients, while extraarticular features significantly improved in 7 of 8 patients. At study entry, 6 of 8 patients were receiving prednisone; at study end, prednisone was discontinued in 3 patients and decreased by more than 50% in the other 3. Overall, there was an 80% reduction in the prednisone dosage. Initially, all patients had anemia, low levels of serum albumin, and an elevated erythrocyte sedimentation rate, while a thrombocytosis was seen in 7 of 8 patients. Serum IgG was initially elevated in 6 patients. IV gamma globulin therapy resulted in a significant increase in hemoglobin and albumin levels and a significant decrease in the mean serum IgG level, platelet count, and erythrocyte sedimentation rate. In only 1 patient did IV gamma globulin fail to significantly improve the clinical or laboratory features of the disease. We suggest that this therapy may be beneficial in the treatment of systemic JRA.

Arthritis, Rheumatoid↗
PubMed1996

All-trans-retinoic acid in POEMS syndrome. Therapeutic effect associated with decreased circulating levels of proinflammatory cytokines.

Chronically elevated serum levels of proinflammatory cytokines is a feature of the syndrome known as POEMS (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal [M] protein, skin changes). A patient had a POEMS syndrome with thrombocytosis and biclonal gammopathy and was treated as follows: all-trans-retinoic acid (tretinoin) at 90 mg/day for 50 days, no treatment for 70 days, readministration of tretinoin at 75 mg/day for 180 days. Focal bone lesion irradiation was performed from day 26 to day 50. Serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha), and IL-1 beta normalized within 7 days after the first administration of tretinoin, transiently increased at the time of radiotherapy, increased again after withdrawal of the tretinoin, and decreased again after its reintroduction. The platelet count and gammopathy paralleled the changes in the cytokine levels. This study documents in vivo the ability of all-trans-retinoic acid to down-regulate the release of IL-6, IL-1 beta, and TNF alpha, and illustrates its potential as a therapeutic agent in conditions associated with chronic overproduction of proinflammatory cytokines.

Cytokines↗
PubMed1981

Thrombotic risks of staging laparotomy with splenectomy in Hodgkin's disease.

No significant excess of deep vein thrombosis (DVT) as measured by the 125I-labelled fibrinogen method was observed in patients having staging laparotomy and splenectomy for Hodgkin's disease (HD) compared with patients having elective cholecystectomy under highly standardized surgical conditions. Patients who did have DVT all had splenic involvement with HD. There was no correlation between the post-splenectomy thrombocytosis and the occurrence of DVT. Patients with non-Hodgkin's lymphoma (NHL) and splenomegaly had a high incidence of DVT after splenectomy.

Adult↗
PubMed1994

Myocardial infarction and polycythemia vera: how should we treat it?

Little is known about the management and treatment of coronary thrombosis in polycythemia vera (PV) [1]. We describe a case of acute myocardial infarction in a patient with recently diagnosed PV and thrombocytosis. The patient underwent emergency catheterization with intracoronary thrombolysis and angioplasty of the left anterior descending coronary artery.

Aged↗
PubMed1986

Transient heart failure in an adult with Kawasaki disease.

Kawasaki disease is a mucocutaneous lymph node syndrome with important cardiovascular complications that usually afflicts young children. We describe a 31-year-old woman who developed transient heart failure during the acute phase of Kawasaki disease. The diagnosis was supported by the presence of all six criteria of the disease: fever, conjunctivitis, strawberry tongue, cervical lymphadenopathies, truncal exanthem, and periungual membranous desquamation. Related clinical and laboratory findings included heart failure, arthralgias, transverse nail grooves, thrombocytosis, and elevated serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and bilirubin. Alternative diagnoses were excluded. During her acute febrile illness, the patient developed tachycardia, hypotension, pulmonary rales, S3 gallop, and hepatojugular reflux. The chest roentgenogram showed new Kerley A and B lines. A first-pass isotopic ventriculography showed diffuse hypokinesia and decreased ventricular ejection fractions; spontaneous recovery occurred after a few days. A coronarography performed two months later showed no aneurysmal dilatation. Kawasaki disease is a cause, albeit rare, of myocardial dysfunction in the adult human, and should be sought for actively in a patient with heart failure during the course of an acute febrile illness, associated with mucocutaneous changes.

Adult↗
PubMed1998

Multivessel coronary thrombosis treated with abciximab (ReoPro) in a patient with essential thrombocythemia.

A 50-year-old man was admitted with acute inferior and anterior myocardial infarction. The patient was diagnosed with essential thrombocythemia (ET) based on the findings of marked thrombocytosis of 1,113 x 10(3)/mm3, splenomegaly, and numerous clumping megakaryocytes on bone marrow biopsy. Emergent coronary angiography revealed extensive multivessel thrombosis involving the left main coronary artery and completely occluding the proximal right coronary artery. In addition to standard therapy with aspirin, heparin, and primary angioplasty of the right coronary artery, the patient received additional antiplatelet therapy with ticlopidine, hydroxyurea, and the platelet glycoprotein IIb/IIIa receptor-inhibiting monoclonal antibody drug abciximab (ReoPro). Serial coronary angiograms 1 and 5 days following the infarction showed progressive thrombus resolution. The pathophysiologic mechanisms and therapeutic challenges of ET-associated coronary thrombosis are discussed in this report.

Abciximab↗