Prevalence Of Thrombocytosis Research Articles

PREVALENCE OF THROMBOCYTOSIS IN ANEMIC PATIENTS OF AKHTAR SAEED TRUST HOSPITAL LAHORE, PAKISTAN

Introduction and objective: Anemia is the one of the most widespread disorder all across the world characterized by low haemoglobin levels in blood causing reduced oxygenation of red blood cells and consequently producing symptoms such as lethargy, malaise and shortness of breath according to its severity. Thrombocytosis is a condition in which the number of platelets is increased and it can be identified by same methods which we use for the diagnosis of anemia. In previous studies, it has been found that thrombocytosis is associated with mild, moderate and severe forms of anemia. The objective of the study is to assess the prevalence of throbocytosis in anemic patients of different ages. Methods: In this cross-sectional study, the patients with anemia who were less than 18 years old were included. Samples were collected from the outdoor and indoor patients of Akhter Saeed Trust Hospital Lahore, who were not treated with any therapy to cure anaemia. About 2-3 ml of venous blood was drawn and sent to laboratory for CBC. Data regarding the MCV, MCH, and platelet count was collected on structured performa. Results: From total 224 patients, 64.73% were males, and 35.27% were females. Statistically, the p-value showed a significant association between all age groups [first (p =0.001), second (p =0.001), third (p =0.001), and fourth (p =0.001)], and genders [males (p =0.001), and females (p =0.001)] with all (mild, moderate and severe) anemias. The prevalence of thrombocytosis in iron deficiency anemia patients was 23.57%. Conclusion: The present study concluded that the patients having anemia can also be affected with thrombocytosis.

Prevalence of thrombocytosis in epidermolysis bullosa patients

Prevalence of thrombocytosis in epidermolysis bullosa patients

Reactive thrombocytosis in malignancy- Can it be a strong predictor for IT

An increased platelet number may be secondary to many conditions. Malignancies are known to induce thrombocytosis in some cases. In patients with malignancies, thrombocytosis has previously been related to disease stage, histological type, and survival. Studies have shown that thrombocytosis is associated with a poor prognosis in various malignancies such as carcinoma ovary, cervical cancer, endometrial cancer, breast cancer and lung cancer. The aim of this study was to analyze the etiology and prevalence of thrombocytosis in malignancy and to assess whether platelet count can be used as a predictor of malignancy in the cases diagnosed as cancer at the time of its first diagnosis. This descriptive study was done on 500 patients with platelet count > 450,000/ μl with the cause being termed reactive. The most common cause of reactive thrombocytosis was Infections (28.8%), Tissue damage (16.4%), Iron deficiency anemia (16.2%), Malignancy (9.6%) and Inflammation (9.4%). Among malignancies, carcinoma oral cavity (20.8%) was found to be more commonly associated with thrombocytosis; with only (4.2%) cases being less than 18 years, rest (95.8%) cases were above 18 years. Thrombocytosis is associated with various neoplasms, therefore it can be used as a diagnostic clue for malignancy in an undiagnosed patient presenting with reactive thrombocytosis and associated symptoms of the disease thus indicating poor outcomes and mortality.

Magnitude of reactive thrombocytosis and associated clinical conditions in dogs

Previous studies on the underlying causes of thrombocytosis have raised scientific interest in its clinical relevance in dogs. The purpose of this study was: (1) to explore the clinical conditions...

Prognostic Value of the Preoperative Platelet-to-leukocyte Ratio for Oncologic Outcomes in Patients Undergoing Radical Cystectomy for Bladder Cancer.

Currently, stratification of patients with bladder cancer (BC) mainly relies on histopathologic and clinical staging. Furthermore, inflammation plays an important role in the pathogenesis of BC. With the preoperative platelet-to-leukocyte ratio (PLR), we introduce a novel prognostic marker based on routine hematologic values in patients undergoing radical cystectomy (RC). In our cohort of 665 patients undergoing RC (2004-2015) for urothelial carcinoma of the bladder (UCB), we analyzed a variety of preoperative hematologic parameters. We investigated the effect of thrombocytosis, leukocytosis, and the PLR on the oncologic outcomes, including cancer-specific survival (CSS), progression-free survival (PFS), and overall survival (OS). Both univariate (log-rank test) and multivariate (Cox regression) analysis were performed. The prevalence of thrombocytosis and leukocytosis and differences in the PLR was assessed using the Mann-Whitney U test. The cutoff levels for leukocytosis, thrombocytosis, and the PLR were defined using receiver operating characteristic curve analysis, with the 5-year CSS as the binary classifier. A PLR of≤ 28 (CSS, P= .033; OS, P= .029) and leukocytosis (CSS, P= .01; OS, P= .001; PFS, P= .003) were significantly associated with adverse oncologic outcomes using the log-rank test. On multivariate regression analysis, the PLR (CSS, P= .022; OS, P= .025) remained a significant prognostic marker among the standard staging variables and hemoglobin level. Advanced BC disease was significantly more prevalent in the patient subgroup with a low PLR (pT2-pT4, 35%; vs. pT≤ 1, 24%; P= .006) and leukocytosis (pT2-pT4, 46%; vs. pT≤ 1, 30%; P< .001; pN+, 49%; vs. pN0, 39%; P< .047). To the best of our knowledge, the present study is the first report of the preoperative PLR as a prognostic factor in patients undergoing RC for UCB. Compared with other inflammatory markers in BC, the PLR can be assessed without additional effort. External validation and its combination with other parameters might improve current prognostication systems for UCB.

Abstract 3404: Thrombocytosis and epithelial ovarian cancer survival: relevant time frame of platelet count measurement and diagnostic threshold for thrombocytosis

Abstract INTRODUCTION: Ovarian cancer is rapidly progressive and lethal disease. Thrombocytosis has been associated with poor prognosis; mechanisms underlying this association include paracrine signaling between platelets and cancer cells, resulting in tumor cell proliferation. However, the relevant timing of platelet measurement in relation to diagnostic operation and a threshold to define thrombocytosis as a prognostic indicator have not been evaluated. METHODS: Tumor Registry confirmed epithelial ovarian and fallopian tube cancer cases with pre-diagnosis platelet counts were identified from the Synthetic Derivative, a de-identified mirror of electronic medical records from the Vanderbilt University Medical Center. Thrombocytosis was defined with two thresholds: platelet count greater than 400 or 450 × 109/L. The relevant time frame of platelet measurement was evaluated within 5 time intervals: on the date of diagnosis, and 1, 2, 4, and 8 weeks before and including the date of diagnosis. Prognostic significance was evaluated using Cox proportional hazards regression to calculate hazard ratios (HR) and confidence intervals (CI); adjustment included age, stage, grade, and histologic subtype of disease. RESULTS: Measured platelet values were available for 136, 241, 280, 297, and 304 cases within the five time intervals. The prevalence of thrombocytosis was 31.6, 39.4, 38.2, 38.1, and 37.5% for 400 × 109/L, and 19.9, 26.1, 25.7, 24.9, and 25.0% for 450 × 109/L across the five intervals, respectively. Thrombocytosis was significantly associated with higher stage and grade, regardless of threshold used. In both unadjusted and multivariable adjusted analysis, thrombocytosis was significantly associated with worse survival. Associations were similar across thresholds and time frames, but were generally larger on the date of diagnosis (HR(400): 1.96, 95% CI 1.23-3.13; HR(450): 1.90, 95% CI: 1.12-3.23), and smaller as time to diagnosis increased up to 8 weeks (HR(400): 1.54, 95% CI: 1.14-2.09; HR(450): 1.55, 95% CI: 1.11-2.15). CONCLUSIONS: Depending upon the threshold used and the timing of measurement, thrombocytosis was identified in 20-40% of epithelial ovarian cancer cases. Regardless of threshold or timing, preoperative thrombocytosis was associated with more aggressive disease characteristics and was an independent negative prognostic factor. These preliminary results support use of a lower thrombocytosis threshold and indicate that platelet count measurements collected up to 8 week preoperatively may be used to inform ovarian cancer prognosis. Citation Format: Gabriella D. Cozzi, Jacob M. Samuel, Jason T. Fromal, Spencer Keene, Marta A. Crispens, Dineo Khabele, Alicia C. Beeghly-Fadiel. Thrombocytosis and epithelial ovarian cancer survival: relevant time frame of platelet count measurement and diagnostic threshold for thrombocytosis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3404.

Prognostic Significance of Preoperative Thrombocytosis in Patients with Endometrial Carcinoma: Our Experience and Review of the Literature

Objective: In this study, we aimed to determine the prevalence and prognostic significance of preoperative thrombocytosis (defined as platelet count ≥ 400 × 103/μl) in patients with endometrial carcinoma. Methods: This was a retrospective analysis of 389 consecutive patients diagnosed and treated at our Institution with endometrial carcinoma between 2004 and 2014. The clinicopathological characteristics of the patients (age, race, tumor type, AJCC stage, and preoperative hematological parameters) were recorded. Survival data were provided by the tumor registry. Results: The mean age of the study population was 63.7 years at diagnosis (range=33 to 97 years), and the majority (n=350, 90%) of patients were Caucasian. Most patients (n=292, 75.1%) were diagnosed with Stage I endometrial carcinoma. In addition, seventeen patients (4.4%) had Stage II, 49 patients (12.6%) had Stage III, and 9 patients (2.3%) had Stage IV disease. The most common type of cancer (n=269, 69.2%) was endometrioid adenocarcinoma, followed by mixed cell (n=16, 4.1%) and serous (n=11, 2.8%) carcinoma, respectively. A small subset (n=24, 6.2%) of the patients had thrombocytosis at diagnosis. The prevalence of thrombocytosis increased with the stage, for example from 4.5% in Stage I to 17.6% Stage II carcinoma. Interestingly, thrombocytosis appeared to be more common in African American patients (30.8%) than in Caucasians (5.4%). Statistical analysis of the survival data revealed an adverse prognostic significance for thrombocytosis: patients with thrombocytosis died at a younger age (64.3 years) than did those with normal platelet count (74.5 years). Conclusion: Thrombocytosis at diagnosis portends adverse prognostic significance in patients with endometrial carcinoma. Elevated platelet count seems to associate with higher stage disease and shorter survival. Thrombocytosis may serve as an independent prognostic factor in endometrial carcinoma or a surrogate marker for high stage disease.

Relationship between thrombocytosis and effect of chemotherapy, prognosis in patients with advanced non-small cell lung cancer

Objective To study the prevalence of thrombocytosis in patients with non-small-cell lung cancer (NSCLC) and its correlation with clinicopathological features. Methods 156 patients with advanced NSCLC were retrospectively analyzed. The platelets degree between the groups with different sex, age, smoking, histological type of advanced NSCLC was compared and analyzed statistically. The relationship between the platelet count and chemotherapy effects was analyzed. Single analysis and Cox regression analysis were used for TTP and OS. Results Compared with the healthy persons, Plt significantly elevated in group with advanced NSCLC (36.5 % , 57/156 vs 5.0 % , 5/100) (P<0.01), and thrombocytosis group responded poorly to chemotherapy (22.8 %, 13/57 vs 39.4 %, 39/99) (P<0.05). The TTP (3.0 months vs 5.2 months) and OS (11.2 months vs 14.2 months) of Plt elevated group were significantly shorter than those of normal group. Conclusion Thrombocytosis is closely related to progress and metastasis of advanced NSCLC. Platelet count can be used as an assistant index in the prognosis judgment of patients with advanced NSCLC. Key words: Carcinoma, non-small-cell lung; Platelet count; Thrombocytosis; Prognosis

Prevalence of thrombocytosis in critically ill patients and its association with symptomatic acute pulmonary embolism

It is uncertain whether thrombocytosis without underlying myeloproliferative diseases is associated with an increased risk of acute pulmonary embolism (PE). We investigated the relationship between thrombocytosis and risk of symptomatic acute PE, and whether Pulmonary Embolism Severity Index (PESI) was reliable in predicting mortality of acute PE. This multicentre registry study involved a total of 609,367 critically ill patients admitted to 160 intensive care units (ICUs) in Australia or New Zealand between 2006 and 2011. Forward stepwise logistic regression was used to assess the relationship between risk of acute PE and platelet counts on intensive care unit (ICU) admission. Acute PE (n=3387) accounted for 0.9% of all emergency ICU admissions. Over 20% of all PE required mechanical ventilation, 4.2% had cardiac arrest, and the mortality was high (14.8%). Thrombocytosis, defined by a platelet count >500x10⁹ per litre, occurred in 2.1% of the patients and was more common in patients with acute PE than other diagnoses (3.4 vs. 2.0%). The platelet counts explained about 4.5% of the variability and had a linear relationship with the risk of acute PE (odds ratio 1.19 per 100x10⁹ per litre increment in platelet count, 95% confidence interval 1.06-1.34), after adjusting for other covariates. The PESI had a reasonable discriminative ability (area under receiver-operating-characteristic curve = 0.78) and calibration to predict mortality across a wide range of severity of acute PE. In summary, thrombocytosis was associated with an increased risk of symptomatic acute PE. PESI was useful in predicting mortality across a wide range of severity of acute PE.

Thrombocytosis in neonates and young infants: a report of 25 patients with platelet counts of ⩾1 000 000 μl−1

Thrombocytosis has been reported in neonates and young infants, but little is known of its prevalence, timing of onset, associated conditions, sequelae and outcomes. To better understand this condition, we used the data repositories of a multi-hospital health-care system to identify all individuals <or=140 days old (20 weeks) who, during the past 6 years, had a platelet count of >or=1000000 microl(-1). We identified all infants with extreme thrombocytosis (using the Sutor definition of a platelet count of >or=1000000 microl(-1)) during the period of January 2003 through December 2008 in any Intermountain Healthcare facility. We obtained the information provided in this report from electronic and paper records. Among 40 471 infants who had one or more platelet counts performed in this period, 25 had extreme thrombocytosis. No cases were identified in the first week after birth, 40% were recognized between the second and fourth weeks and 40% between the fifth and eighth week. The prevalence of thrombocytosis had no relationship with birth weight or gestational age but a slight predominance of female patients (15/25) was noted. In all, 26 episodes were found among the 25 infants: 12 episodes involved an antecedent infectious disease, 8 had an antecedent surgical procedure, 4 had the anemia of prematurity and 1 each had congenital adrenal hyperplasia and opiate withdrawal syndrome. No pathological thromboses or hemorrhages or other sequelae were detected and all episodes resolved with no deaths. The thrombocytosis cases that we report were all consistent with reactive thrombocytosis (also known as secondary thrombocytosis); none seemed to be essential (primary) thrombocytosis. We speculate that the pathogenesis involves increased platelet production due to megakaryopoietic stimulators induced by an infectious or inflammatory condition. From this series and previous reports, young infants with platelet counts up to 1300000 microl(-1) do not seem to have a significant risk of thrombotic or hemorrhagic problems, and do not generally require anti-platelet or cytoreductive treatment.

Thrombocytosis in Iron Deficiency Anemia: What the Primary Care Physician Needs To Know.

The prevalence of reactive thrombocytosis in iron deficiency anemia (IDA) as well as it's duration and need of further work up is not always known by primary care physicians (PCP). The data we know came mainly from papers published back in the 1960's involving small sample sizes, most of which consisted of pediatric patients. The most widely cited publication is based on Schloesser's 1965 review of 46 iron deficient anemic adult patients (Hb <11, Serum iron <70ug per 100ml), of which 60.8% exhibited thrombocytosis. Thrombocytopenia (28.3%) among IDA patients was described by Gross in his 1964 publication. Most of the studies failed to address the mechanism linking thrombocytosis and IDA, Endogenous erythropoietin (EPO) levels are high in IDA and were not available in 1960 therefore we decided to examine any statistically significant relationship between platelets counts and EPO levels. The relationship between platelets, hemoglobin (Hb) and ferritin were also evaluated.A comprehensive chart review of 450 patients with a diagnosis of anemia between 2002 and 2006 was performed. These patients were screened for iron deficiency anemia using the following criteria: Hb ≤ 12 for women and Hb ≤ 14 for men, ferritin ≤ 20. Anemias other than IDA were excluded by identifying patients with concomitant infectious disease, malignancy, pregnancy or with high CRP levels indicative of inflammatory process. Sample size 140 patients. Pre and Post treatment lab data consisting of Hb, Plt, endogenous EPO, Ferritin and Reticulocyte were collected.Results see (table 1).31% of our patients (43 / 140) experienced thrombocytosis. We found a statistically significant correlation between Hb levels and plt counts. R = −0,299 .p < 0.05. however a cause effect relationship was not established. We were not able to find a significant relationship between platelets counts and EPO levels or Ferritin levels.In 65.6 % of our patients thrombocytosis resolved in 28 days or less. (See table 2)The prevalence of thrombocytosis in our series 31% differs from the previous published data. Extreme thrombocytosis was not frequent in our series, none of our patients presented with thrombocytopenia. To our knowledge this is the largest sample size surveyed for such study. A mechanism to explain thrombocytosis in IDA remains unclear but according to our data is not related to either the iron cellular concentration (ferritin) or endogenous erythropoietin level. We recommend that patients with IDA related thrombocytosis should be followed with a CBC 4 weeks after treatment was started. No other work up for thrombocytosis seems to be necessary in the presence of diagnosed IDA. Persistent or increasing thrombocytosis should be followed closely and underlying bone marrow disorder such as myelodysplastic disorders considered as a differential after 4 weeks of complied treatment.Thrombocytosis in IDA (Results)n=140Female 98%Male 2%RangeMeanAge18 – 8842Hemoglobin4.2 – 11.78.7MCV50.6 – 92.770.2Ferritin1– 206.8Platelets170 – 1,046.000410EPO14.6 – 4272295Extreme thrombocytosis (Plt > 1000K 1/140 (0.7%)Time needed to resolve thrombocytosis (post treatment)Number of DaysNumber of Patients (%)1 – 76 (18.8%)8 – 147 (21.9%)15– 214 (12.5%)22 – 287 (21.9%)29–351 (3.1%)35 +7 (21.9%)Total (range 6–153)32Average of 28.7 days to resolve thrombocytosis (post treatment)

Diagnostic significance of platelet count and other blood analyses in patients with lung cancer

The objective of this study was to evaluate the clinical value of an elevated platelet count and other routine laboratory tests for predicting malignancy in patients with radiologically suspected lung cancer. Platelet count, haemoglobin, total leukocyte count, erythrocyte sedimentation rate (ESR) and serum lactate dehydrogenase (LDH) were analysed in 126 prospectively admitted patients with suspected lung cancer. The patients were divided by pathologic diagnosis into those with benign disorders (n=65) and with malignancies (n=61). Patients with lung cancer were staged (TNM) and the tumours were classified according to histological types (WHO). Thrombocytosis (platelet count >400x10(9)/l) was present in 8% (5/65) of patients with benign disease and in 57% (35/61) of patients with malignant disease (p<0.00001). The prevalence of thrombocytosis in patients with primary lung cancer was 53% (27/51). Elevated platelet count was more common in advanced disease (stage III and IV). No difference was observed between histological types. The sensitivity of thrombocytosis for predicting malignancy was 0.57 and the specificity 0.92. When elevated platelet counts, LDH and ESR were combined, a sensitivity of 0.71 and a specificity of 1.00 was achieved. The positive and negative predictive values were 1.00 and 0.89, respectively. Elevated platelet count is frequently observed in patients with lung cancer. When test results of platelet count and other routine blood analyses are combined, a high sensitivity and specificity for predicting malignancy can be achieved. These tests are clinically useful in the evaluation of patients with radiologically suspected lung cancer.

Poor prognosis associated with thrombocytosis in patients with gastric cancer.

Thrombocytosis is commonly associated with malignant disease and has recently been suggested to be a poor prognostic indicator in patients with lung cancer and gynecological cancers. The prevalence of thrombocytosis in patients with gastric cancer was reviewed, and its association with poor prognosis was investigated. Platelet count (PLT) and hemoglobin concentrations (Hb) were reviewed in 369 consecutive patients with histologically verified gastric cancer from 1994 to 2000. Differences between categories were analyzed with analysis of variance, and survival was compared by using the log-rank test on the Kaplan-Meier life table. Multivariate Cox regression analysis was used to evaluate whether thrombocytosis is an independent prognostic marker. Thrombocytosis was found in 42 patients, and anemia was found in 200 patients. PLT was negatively correlated with Hb. Mean PLT was significantly increased in patients with noncurative operations. There was a positive correlation between the depth of tumor invasion and PLT. One- and 3-year survival expectancies in patients with or without thrombocytosis were 52.4% and 23.4% and 85.7% and 72.9%, respectively. PLT was identified as an independent prognostic factor after lymph node metastasis and depth of tumor invasion. Thrombocytosis is an independent prognostic indicator of survival in patients with gastric cancer.

Thrombocytosis With Sideroblastic Erythropoiesis: A Mixed Myeloproliferative Myelodysplastic Syndrome

Some patients with haematological neoplasms have features which overlap between a myelodysplastic syndrome and a myeloproliferative disorder. Two such patients are reported, both having sideroblastic erythropoiesis and thrombocytosis and one sequentially developing features of atypical chronic myeloid leukaemia, idiopathic myelofibrosis and acute megakaryo-blastic leukaemia. The prevalence of thrombocytosis among cases of refractory anaemia with ring sideroblasts may be as high as 15–20% and has implications for choice of therapy.

Elevated platelet count in patients with endometrial carcinoma: correlation with selected prognostic factors and with survival

Platelets may play a role in the metastatic process and, among gynecologic malignancies, thrombocytosis has been reported in cervical and ovarian malignancy. The present study was conducted in order to assess the prevalence of thrombocytosis in endometrial carcinoma and to correlate platelet count with prognostic factors and with survival. The prevalence of preoperative thrombocytosis was assessed in 66 endometrial carcinoma patients and their platelet count was correlated with selected prognostic factors and with projected survival. The prevalence of thrombocytosis ( 400 000 µL−1) was low (one of 66 patients) compared with that in cervical and ovarian carcinoma. Nevertheless, a significant (P = 0.032) correlation was found between an elevated ( 300 000 µL−1) platelet count and unfavorable grade of differentiation. Patients with an elevated count also had a poorer survival rate and a higher prevalence of older age, high stage and deep myometrial invasion, but this trend did not reach statistical significance. The combination of unfavorable grade and an elevated platelet count had a higher specificity and positive predictive value for deep myometrial invasion than unfavorable grade alone. The prevalence of thrombocytosis in endometrial carcinoma is low. An elevated platelet count may have some prognostic significance, but its ultimate role in endometrial carcinoma remains to be elucidated.

Significance of thrombocytosis in patients with epithelial ovarian cancer

Abstract OBJECTIVES: Our objective was to determine the relevance of a preoperative platelet count in ovarian cancer. Special interest was directed to a possible prognostic significance of thrombocytosis in this disease. STUDY DESIGN: Charts of 130 patients with epithelial ovarian cancer were reviewed retrospectively. Survival analyses were performed with the Kaplan-Meier method. Differences in survival were examined according to Mantel and Breslow. Platelet counts were furthermore correlated to other clinical parameters. For this purpose the Spearman rank test and a stepwise logistic regression model were used. Data comparison was accomplished with the Mann-Whitney U test and the χ 2 test. RESULTS: Prevalence of thrombocytosis was 38%. No differences in survival between patients with or without thrombocytosis was found. Volume of ascities and hemoglobin concentrations were independently associated with thrombocytosis ( p = 0.002 and p=0.004, respectively). CONCLUSIONS: Thrombocytosis is not a useful prognostic factor in ovarian cancer. Elevated platelets are predominately associated with the presence of ascites and marked anemia. (AM J OBSTET GYNECOL 1994;170:549-54.)

Significance of thrombocytosis in patients with epithelial ovarian cancer

OBJECTIVES: Our objective was to determine the relevance of a preoperative platelet count in ovarian cancer. Special interest was directed to a possible prognostic significance of thrombocytosis in this disease. STUDY DESIGN: Charts of 130 patients with epithelial ovarian cancer were reviewed retrospectively. Survival analyses were performed with the Kaplan-Meier method. Differences in survival were examined according to Mantel and Breslow. Platelet counts were furthermore correlated to other clinical parameters. For this purpose the Spearman rank test and a stepwise logistic regression model were used. Data comparison was accomplished with the Mann-Whitney U test and the χ 2 test. RESULTS: Prevalence of thrombocytosis was 38%. No differences in survival between patients with or without thrombocytosis was found. Volume of ascities and hemoglobin concentrations were independently associated with thrombocytosis (p = 0.002 and p = 0.004, respectively). CONCLUSIONS: Thrombocytosis is not a useful prognostic factor in ovarian cancer. Elevated platelets are predominately associated with the presence of ascites and marked anemia. (AM J OBSTET GYNECOL 1994;170:549-54.)