Anesthesia in two patients with essential thrombocythemia

Case 1. The patient was a 69-year-old man with essential thrombocythemia (ET), who underwent urgent laparotomy. On admission he was dehydrated and the platelet count was more than 160 x 10(4).microliter-1, with hematocrit of 50%. Anesthesia was induced with ketamine i.v. and maintained with nitrous oxide and sevoflurane in oxygen. Postoperative care included the administration of gabexate mesilate (GM) which is an antiplatelet agent. Case 2. An 84-year-old woman with ET was diagnosed as gastric cancer and elective gastrectomy was scheduled. The platelet count was more than 100 x 10(4).microliter-1. The patient was anesthetized with nitrous oxide and oxygen supplemented with fentanyl and mepivacaine via epidural catheter. Intravenous infusion of GM was performed at a rate of 1 mg.kg-1.hr-1 during surgery. PF-4 and beta-TG were measured. These are platelet releasing factors. The level of PF-4 decreased to normal level during this procedure. In conclusions, it will be important to use GM during anesthesia in order to avoid the complications such as myocardial or pulmonary infarction caused by thrombocythemia.     

Myelodysplastic transformation in a case of essential thrombocythemia treated with pipobroman

A report of an 87-year-old Caucasian female with an extensive sebaceous carcinoma of the parotid gland is presented. The computed tomographic characteristics of this rare neoplasm are reported for the first time.     

Reduced in vitro clot lysis and release of more active platelet PAI-1 in polycythemia vera and essential thrombocythemia

The accuracy of image to patient registration is a critical issue in the intraoperative use of frameless stereotaxic instruments for surgical guidance. This study was performed to assess the accuracy of image to head phantom registration using several standard registration techniques and a clinical frameless stereotaxic instrument. Two types of radioopaque fiducial markers were fixed to a plastic head phantom, and a computed tomography scan of the phantom was performed in the routine fashion. Image to phantom registration was carried out using fiducial markers, fiducial markers plus surface fit, anatomic landmarks, and anatomic landmarks plus surface fit. After each registration, linear inaccuracy measurements were performed for each of 32 markers. Each registration was performed 10 times, and the overall mean error measurements and anterior and posterior error were computed and compared. The overall mean error was smallest for the fiducial registration alone (2.07 mm). The magnitude of error increased significantly for posterior locations for all other registration techniques, but it was not significantly increased for the fiducial registration method. For this hardware configuration, registration with surface-applied fiducial markers is measurably more accurate than registration with surface anatomic landmarks. The addition of surface points to the fiducial registration does not increase the registration accuracy but, in fact, increases the degree of error.     

Acute coronary occlusion and in-stent thrombosis in a patient with essential thrombocythemia

BACKGROUND: Physical activity in old age probably protects against hip fracture. However, very little is known about the impact of occupation during working life, in terms of its physical activity level and the socio-economic status (SES) it indicates, on the risk of hip fracture in later life. METHOD: A population-based case-control study was conducted on 416 subjects to investigate relationships between risk of hip fracture and occupational physical activity and occupation-related SES. Occupational physical activity was coded according to the proportion of the working day at ages 20 and 50 years that the subjects were likely to have spent sitting. The Australian Classification of Standard Occupations (ASCO) was used as the basis for the coding of SES, indicated by job titles. RESULTS: Compared with those in the intermediate category, women with a sedentary job at age 50 years (odds ratio (OR) 7.2, 95 per cent confidence interval (CI) 1.2-41.9) or a mainly weight-bearing job (OR 5.1, 95 per cent CI 1.1-23.2) had an increased risk of hip fracture. A decreasing hip fracture risk with increasing SES of the longest held job was also observed. CONCLUSION: The finding of a J-shaped relationship in women between occupational physical activity and risk of hip fracture supports the need for research into the most effective types of exercise for maintenance of bone strength. Furthermore, the protective effect of SES demonstrated in this study still need to be corroborated in other studies before establishing evidence of a causal relationship.     

Acquired von Willebrand disease in patients with high platelet counts

Operative indication and risk factors for unruptured cerebral aneurysms were discussed. During the past 11 years, 38 aneurysms in 33 patients with a mean age of 54 years were operated on. All aneurysms were located in the anterior circulation; 16 were of carotid artery, 15 of the middle cerebral artery, 4 of the anterior communicating artery, and 3 of the distal anterior cerebral artery. Six cases (18.2%) developed neurological deficits postoperatively. The deficits were permanent in 3 cases (morbidity 9.1%). There was one operative death (mortality 3.0%). Operative risk factors were analyzed in 4 particular cases. Of these 4 cases, two cases had large aneurysms (14 and 16mm in diameter) located at carotid-ophthalmic and at the inferior wall of the carotid arteries, respectively. One developed unilateral blindness possibly due to operative manipulation, and the other showed hemiparesis with aphasia due to postoperative carotid stenosis caused by clipping. Of the rest 2 cases; one with multiple (carotid and middle cerebral) aneurysms developed hemiparesis because of postoperative stenosis of the atheromatous parent artery caused by clipping, and the other, with a large (17mm) aneurysm at the distal anterior cerebral artery, died of postoperative intracerebral hematoma. Both of these cases were associated with cerebral ischemic disease. All cases that developed postoperative neurological deficits had varying degrees of hypertension. Reviewing our series and other reports, it can be said that age is one of the most important factors that influence operative mortality. However, a lower risk of rupture develops as age increases. For those under 70 years of age, operation is considered safe in healthy individuals, especially among those without hypertension. However, in cases where there are large aneurysms, multiple lesions, less accessible locations and cerebral ischemic disease, operative risks should be kept in mind. Operative morbidity in these cases is relatively high compared to that found among others. Therefore, planning a meticulous surgical strategy and further careful operative manipulation are essentials, when surgical treatment is indicated.     

Screening for renovascular hypertension in a population with relatively low prevalence

OBJECTIVE: To evaluate the accuracy and cost-efficacy of the diagnostic procedure and treatment for renovascular hypertension. SETTING AND PATIENTS: A total of 519 patients referred to the university clinic for hypertension were screened for renovascular hypertension with 405 captopril challenge tests (CCT) and 450 captopril renographies (CRG). INTERVENTIONS: Abdominal angiography was performed on 84 patients for positive screening. Fifteen patients underwent angiography for a sole suspicious clinical presentation. The angiography revealed 17 renal artery stenoses and five occlusions in 20 patients. Fifteen technically successful angioplasties and three nephrectomies were performed. RESULTS: In the patients who underwent angiography, CCT had a specificity of 39% and a sensitivity of 67% for renovascular hypertension. CRG had a sensitivity of 100% and a specificity of 68%. In the whole study population, the estimated specificity of CCT was 88% and that of CRG 95%. Invasive treatment reduced systolic/diastolic blood pressure from 157/99 to 140/87 mmHg and the number of antihypertensive drugs used from 2.6 to 1.4 in 16 patients (mean age 49 years). Angiotensin converting enzyme (ACE) inhibition was effective in four elderly patients. Cost-efficacy analysis Screening with CRG and invasive treatment cost US$15400 per successful invasive treatment Equally effective pharmacological treatment would have cost US$10400. Limiting the screening with CRG to the 173 patients with no obvious renal parenchymal disease and with hypertension at a younger age (< or =30 years) or unresponsive to two antihypertensive drugs (diastolic blood pressure > 90 mmHg) would have yielded a prevalence of 12% and missed only one elderly patient who responded to ACE inhibition. The limited screening, along with invasive treatment, would have cost US$7300 per patient CONCLUSIONS: CRG is superior to CCT for screening of renovascular hypertension. Screening with CRG is cost-effective when limited to patients with no obvious renal parenchymal disease and with hypertension that does not respond to two antihypertensive drugs or is detected in patients no older than 30 years.     

Aspirin in essential thrombocythemia: status quo and quo vadis

Aspirin has a well established role in the prevention of arterial thrombosis. Discussion on the efficacy and safety of aspirin in the treatment and prophylaxis of thrombosis in essential thrombocythemia (ET) has become an important issue. The rationale for its use in ET comes from the observation that arterial thrombosis and platelet-mediated microcirculatory disturbances are the major causes of morbidity and mortality in ET. Experimental data have shown persistently elevated levels of thromboxane A2 (TXA2) in ET patients probably reflecting an enhanced in vivo platelet activation. Increased TXA2 biosynthesis and platelet activation in vivo in ET are selectively suppressed by repeated low doses of aspirin. ET-related symptoms such as erythromelalgia, transient neurologic and ocular disturbances are sensitive to aspirin. However, the benefit of low-dose aspirin is still uncertain in the primary prevention of thrombosis in ET. Furthermore, aspirin may unmask a latent bleeding diathesis frequently present in ET which may result in severe hemorrhagic complications. Thus, aspirin is contraindicated in ET patients with a bleeding history or a very high platelet count (> 1500 x 10(9)/L) leading to the acquisition of von Willebrand factor deficiency. If indicated, aspirin is presently used in the widely accepted low-dose regimen of 100 mg daily. However, an optimal effective dose has not yet been established. To further evaluate the efficacy and safety of aspirin in ET, prospective clinical trials are needed.     

Spurious platelet counts in acute leukaemia with DIC due to cell fragmentation

Automated platelet counts in a patient with newly diagnosed AML M5 with extreme leukocytosis were reported as 129, 166 and 121 x 10(9)/1. Routine blood films showed a corresponding number of platelet-sized particles, judged to be platelets. The patient was treated for DIC with low-dose heparin infusion. Platelet transfusions were not given initially. The patient died 14 h after admission from intracerebral haematoma. The origin of the platelet-sized particles seen in routine stained blood films was examined by cytochemical and immunological staining for peroxidase, non-specific esterase, CD 13 and CD 33. About 1/3 of the fragments had the same staining characteristics as the leukaemia cells, indicating leukaemia cell origin. Staining for platelet-specific antigen GpIIIa was positive only in 4% of the platelet-sized fragments, with a calculated true platelet count of 4 x 10(9)/1. The presence of cell fragments masquerading as platelets should be suspected in leukaemia patients with bleeding symptoms and normal or near normal platelet counts.     

Surgery for cholecystocholedocholithiasis in a patient with asymptomatic essential thrombocythemia: report of a case

Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by a remarkable increase in the platelet count and various clinical symptoms. The perioperative management of patients with ET has yet to be determined, especially when there are no clinical symptoms. We report herein the case of a woman with gallstones whose preoperative hematological data showed remarkable thrombocythemia, but her coagulation studies were normal. The Philadelphia chromosome was negative and bone marrow cytology showed a marked increase in megakaryocytes. Surgery was performed under a diagnosis of cholelithiasis with ET. Considering her severe thrombocythemia and obesity, sufficient heparin was administered to prevent deep vein thrombosis; however, this precipitated postoperative bleeding, necessitating a reoperation. A functional abnormality of the patient's platelets was suspected, and the aggregation by adenosine diphosphate was subsequently found to be significantly inhibited. As patients having ET with no symptoms might have depressed platelet aggregability despite remarkable thrombocythemia, when abdominal surgery is performed, prophylactic therapy for deep vein thrombosis should be avoided. Hence, the preoperative aggregation study of platelets might offer useful information about whether postoperative antithrombotic therapy is indicated.     

Neurologic and visual symptoms in essential thrombocythemia: efficacy of low-dose aspirin

We have shown that oestrogen has a central integrative role in regulating key components of the progesterone biosynthetic and corticosteroid metabolic pathways within syncytiotrophoblasts that govern placental function and maturation of the fetal pituitary-adrenocortical axis. Studies utilizing classic binding procedures and RNAse protection have demonstrated that human placental villous tissue exhibits specific high affinity oestrogen binding and expresses the mRNA for the oestrogen receptor. However, it is not known whether the oestrogen receptor is expressed specifically in syncytiotrophoblasts. Therefore, the present study determined whether the oestrogen receptor protein was detectable by immunocytochemistry in cultured human syncytiotrophoblast maintained in a low oestrogen/progestin environment. Cytotrophoblasts were isolated from human term placentae by trypsin dispersion and Percoll gradient centrifugation and cultured for 5, 7 or 10 days. Incubation of syncytiotrophoblast with 5-10 micrograms/ml of the anti-oestrogen receptor rat monoclonal antibody D-75, which is specific for the primate oestrogen receptor, resulted in identification of the oestrogen receptor in the nuclei of these cells. In contrast, there was no reactivity of the trophoblasts to either rat IgG or an irrelevant rat monoclonal antibody IgG2a against mouse common leukocyte antigen T200. Collectively, these findings indicate that oestrogen receptor is expressed in the nuclei of human placental syncytiotrophoblasts and support the suggestion that the syncytiotrophoblast is an oestrogen-responsive tissue.     

Quantitative changes in platelet counts following major urological pelvic surgery

From 1986 to 1990, a multicentric phase II study was conducted with pirarubicin, a new semi-synthetic anthracyclin[4'-O-tetrahydropyranyl-adriamycin (THP)]. 87 patients with advanced gynaecological cancers were treated: epidermoid cervical carcinoma (n = 31), adenocarcinoma of the endometrium (n = 28) and ovarian adenocarcinoma (n = 28). THP was administered by short intravenous infusion, for 3 consecutive days, every 3 weeks. The initial dose of THP was 25 mg/m2 day (25% of patients) which was then reduced to 20 mg/m2 day. The average number of courses was 3.7 (range 1-10). The cumulative THP dose was 180 mg/m2 (range 56-594) in cervix and endometrial tumours and 121 mg/m2 (range 58-425) in ovarian tumours. Myelosuppression was the major observed toxicity with grade 3-4 leukopenia and thrombocytopenia in 62 and 19% of the patients, respectively. Severe general complications occurred in 6% of the patients with three fatalities due to infections. Gastro-intestinal side-effects were frequent and usually mild (7% of grade 3 vomiting). 48% of the patients showed alopecia, which was complete in 9 cases (10%). 3 patients experienced cardiac events. No significant antitumoral activity was observed in patients who had failed to respond to previous chemotherapy. Promising antitumoral activity was noticed in untreated cervico-uterine carcinomas with 19% partial responses and 12% complete responses (CR). THP activity was lower in endometrial carcinomas (9.5% CR). Results were found to be negligible in ovarian cancer patients, most of them being refractory to previous chemotherapy containing an anthracyclin compound. On the basis of these results, the definite role of THP in gynaecological cancers deserves to be studied in more favourable programmes (e.g. in combined protocols as first-line chemotherapy).     

Development of essential thrombocythemia in a patient treated with interferon alfa and pentostatin for hairy cell leukemia

A patient is reported who developed essential thrombocythemia after successful treatment for hairy cell leukemia. He was initially treated with interferon alfa and subsequently relapsed within one year of treatment. His diagnosis was reconfirmed and then treated with Pentostatin. Six years after treatment he had a progressive increase in the platelet count and was diagnosed as essential thrombocythemia. Second cancers including various types of hematological malignancy have been reported in patients with hairy cell leukemia treated with chemotherapy or interferon alfa. These malignancies may represent either a new clonal disorder or a complication of drug treatment. This is the first report of a chronic myeloproliferative disorder following successful treatment of hairy cell leukemia.     

Effect of relatively low dose amiodarone therapy on left ventricular function in patients with ventricular tachyarrhythmias

The effect of oral amiodarone (AMD) therapy on left ventricular (LV) function was evaluated retrospectively in Japanese patients with ventricular tachyarrhythmias and congestive heart failure. Seventeen patients were treated with oral AMD (maintenance dose 191+/-52mg/day) for more than 12 months. Fractional shortening (FS) on echocardiography revealed a trend towards an increase in the short-term (3 months) (p=0.06), but was not significant in the long-term follow-up period (more than 12 months) after AMD therapy. In 8 patients with 1 episode of myocardial infarction, FS revealed a trend towards an increase (p=0.09). In all of the 4 patients with dilated cardiomyopathy whose LV end-diastolic diameter was increased, FS was decreased in the long-term follow-up. Neither hospitalization frequency nor New York Heart Association classification were reduced by AMD therapy. In conclusion,oral AMD therapy did not cause LV function to recover significantly and could not improve the clinical course in patients with ventricular tachyarrhythmias. However, if the underlying disease is not progressive, AMD therapy may improve LV function.     

Evidence for altered platelet nitric oxide synthesis in essential hypertension

OBJECTIVES: To determine whether platelet aggregation to collagen was abnormal in patients with essential hypertension and whether nitric oxide donors and inhibitors of nitric oxide synthesis affect platelet aggregation differently in hypertensives compared with healthy controls. DESIGN: Platelet aggregation assays were conducted ex vivo from both hypertensive and normal subjects simultaneously. METHODS: Platelet aggregation in response to collagen was measured in platelet-rich plasma from 16 patients with untreated essential hypertension and 16 healthy volunteers matched for age, sex and smoking habits. The effect of sodium nitroprusside (a nitric oxide donor) and NG-monomethyl-L-arginine (L-NMMA), a specific nitric oxide synthase inhibitor, was studied. RESULTS: In healthy controls L-NMMA caused a marked increase in platelet aggregation, whereas in hypertensive patients a small inhibition of aggregation was seen. This was significantly different from the response seen in normal controls. No difference was seen in the aggregatory response to collagen between hypertensive patients and healthy controls. Sodium nitroprusside caused inhibition of aggregation in hypertensive patients and in controls, but there was no significant difference in the degree of inhibition between the two groups. CONCLUSIONS: We conclude that in platelets from hypertensive patients there is a markedly reduced sensitivity to L-NMMA, which could be explained by a reduction in nitric oxide synthesis.