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Diagnosis of essential thrombocythemia at platelet counts between 400 and 600x10(9)/L. Gruppo Italiano Malattie Mieloproliferative Croniche(GIMMC).

BACKGROUND AND OBJECTIVE: Diagnostic criteria for essential thrombocythemia (ET) remain essentially negative, that is, exclusion of other myeloproliferative diseases and causes of reactive thrombocytosis. A platelet count above 600x10(9)/L is still generally considered an absolute diagnostic criterion although new protocols for positive diagnostic criteria have recently been proposed, reducing the stringency of a definite platelet limit. This study demonstrates that a platelet count 600x10(9)/L is not a reliable diagnostic criterion for ET, especially in the early stages. DESIGN AND METHODS: An ongoing retrospective study by the GIMMC analyzed 2,316 ET patients diagnosed between 1986 and 1995. Of these 2,316 patients, diagnosed according to the PVSG criteria, 68 had a platelet count 600x10(9)/L and were analyzed separately; 37 out of 68 were excluded from this analysis because of a follow-up shorter than 2 years and/or because of treatment with myelosuppressive agents. The remaining 31 patients were the subjects of our study. RESULTS: After a median follow-up of 4.56 years (range 2-9.6 years) none of the 31 patients had a spontaneous decrease of platelets to the normal range. Transformation to a different chronic myeloproliferative disorders was never observed and no patient developed a condition known to produce reactive thrombocytosis. During follow-up, 23 patients (74%) were treated with anti-aggregating drugs, mainly aspirin. The disease did not evolve into acute leukemia in any patient, 1 had a thrombotic event and none presented hemorrhagic episodes. Median platelet count during follow-up was 534x10(9)/L (range 398-997x10(9)/L). INTERPRETATION AND CONCLUSIONS: Long term follow-up has documented that our 31 patients were correctly diagnosed as having ET, although platelet count was 600x10(9)/L. Our patients were probably in a early phase of their disease and following updated PVSG criteria would have been misdiagnosed leading to incomplete recognition of the natural history of the disease. Further, because an early diagnosis could also have a clinical relevance, our results outline the need for new criteria for the diagnosis of ET. The exclusion of patients with a platelet count between 400 and 600x10(9)/L may prevent patients, nevertheless at risk of vascular complications, from being treated.

Adolescent↗

Improving guideline compliance: assessment of unit-based reminder for monitoring platelet counts post-PCI.

In assessing our institution's vascular access site bleeding complication rate, we found (anecdotally) that for many patients platelet count was not measured according to recommendations of the manufacturer of the predominantly used glycoprotein (GP) IIb/IIIa agents, in either the catheterization recovery unit (CRU) or the coronary care unit (CCU). We hypothesized that a unit-focused effort to remind cardiologists to order platelet counts after percutaneous coronary interventions GP IIb/IIIa would improve compliance. Findings indicated that a greater number of patients had platelet counts drawn after a reminder effort had been implemented. For both the first and second draws, the CCU had a higher pre-reminder rate than the CRU. Post-reminder, the CCU had no significant changes, whereas the CRU showed significant increases in both the first and second draws. For post GP IIb/IIIa platelet measurement, aggregate analysis (CRU and CCU) showed that, of those patients who had platelet counts drawn pre-reminder, only 18.2% met the first guideline and only 17.1% met the second. Post-reminder results showed no significant changes for the first or second draws. We concluded that the practical application of a standard operating procedure can have a secondary beneficial effect despite not meeting the stringent parameters set in prescribing guidelines.

Aged↗

Comparison of platelet counts in first and second newborns of mothers with immune thrombocytopenic purpura.

OBJECTIVE: This study was designed to estimate the predictive value of the first neonatal platelet count for the second neonate in women with immune thrombocytopenic purpura (ITP). METHODS: Data of 34 patients, repeatedly pregnant while they had ITP, were prospectively collected in two study centers between 1984 and 1995. The main outcome measure was neonatal thrombocytopenia. RESULTS: Early neonatal platelet counts (i.e., umbilical cord count or count during the first 24 hours of life) between siblings were correlated (r = .73; 95% confidence interval (CI) for the correlation coefficient 0.52, 0.86). Severe thrombocytopenia (less than 50 x 10(9)/L) at birth did not occur in any of the 27 siblings of infants with birth platelet levels above 50 x 10(9)/L. Also the second sibling's nadir neonatal platelet counts during the first 2 weeks of life were correlated with those of the first sibling (r = .76; 95% CI for the correlation coefficient 0.58, 0.88). In those cases in which the first sibling had a lowest platelet count above 100 x 10(9)/L (n = 19), the second sibling never became thrombocytopenic. CONCLUSION: The platelet count of the first sibling can be used to counsel women with ITP, and may be helpful in their management.

Female↗

Precipitous fall in platelet count with anagrelide: case report and critique of dosing recommendations.

Thrombotic and hemorrhagic events may result from high circulating concentrations of platelets (> 1,000,000/mm3), and measures to reduce the platelet count are indicated in symptomatic or extreme thrombocytosis. The platelet count can be decreased quickly by plasmapheresis, but the effect is transient. Patients with thrombocytosis secondary to a myeloproliferative disease, such as chronic myelogenous leukemia (CML), frequently require more sustained suppression of the platelet count. Hydroxyurea, busulfan, and interferon are used to maintain a lower platelet count but are occasionally ineffective or intolerable. An alternative to these therapies is anagrelide, a quinazolin derivative that was approved by the Food and Drug Administration in March 1997. Because current dosing guidelines for anagrelide are scarce, the dosing method of the Anagrelide Study Group that published the largest study to date on the drug's efficacy in thrombocytosis was followed. Two unexpected episodes of anagrelide-induced thrombocytopenia occurred despite following these dosing methods. This prompted a critical evaluation of the pharmacodynamic response and the appropriateness of anagrelide dosage recommendations. A case of thrombocytosis treated with anagrelide in a patient with CML is described.

Adult↗

Platelet count and disease activity in juvenile rheumatoid arthritis.

Blood samples from 41 children with juvenile rheumatoid arthritis (JRA) were studied. The platelet count was tested for possible relationship and correlation with a number of clinical and laboratory parameters. High platelet count was associated with active disease, presence of secondary amyloidosis, and poor functional capacity. The platelet count was positively correlated with the erythrocyte sedimentation rate, anemia, and granulocytosis. The platelet count thus seems to provide an additional parameter of disease activity in patients with JRA.

Adolescent↗

Racial differences in platelet counts in New Zealand men.

Healthy Maori males were found to have higher platelet counts (mean 295 x 10(9)/L: SD 46) compared to healthy nonMaori males (mean 253 x 10(9)/L; SD 50). Maori males had higher weights (mean 88.4 kg; SD 12.5) than nonMaori males (mean 81.0 kg; SD 9.0); and the platelet count was significantly correlated with weight (r = 0.30; p = 0.003). After weight adjustment significant differences between Maori and nonMaori males for platelet counts remained. These findings have implications for laboratory reference ranges, and may be of epidemiological significance in cardiovascular disease.

Adult↗

The effects of infusion methods on platelet count, morphology, and corrected count increment in children with cancer: in vitro and in vivo studies.

PURPOSE/OBJECTIVES: To determine whether infusion method influences the quality of platelets transfused. DESIGN: Linked in vitro and in vivo study. Quasi-experimental design for in vitro and cross-over design with balanced randomization for in vivo. SETTING: Pediatric cancer center in the midsouthern United States. SAMPLE: Pheresed/pooled platelet units in vitro (n = 12). In vivo convenience sample of 26 children, ages 2-19 years, with cancer and thrombocytopenia who required platelet transfusion. METHODS: Two infusion pumps (IMED 980 and Gemini, IMED Corp., San Diego, CA) versus gravity flow for in vitro platelet infusion. Gemini infusion pump versus gravity flow for in vivo platelet transfusion. MAIN OUTCOME MEASURES: Platelet count, morphology score, and corrected count increment. FINDINGS: No significant differences noted in platelet count or morphology score among or across the three infusion methods in vitro. No significant differences noted between the two infusion methods in platelet count or corrected count increment in vivo. CONCLUSIONS: Although limited to a specific patient population, setting, and infusion device, findings revealed that the pump was clinically acceptable because it did not negatively affect platelet recovery. Replication of this study with other infusion devices is recommended. IMPLICATIONS FOR NURSING PRACTICE: Study findings validate the current nursing procedure for the administration of platelets at the study setting. Use of infusion pumps for platelet transfusions is time-efficient and energy-efficient for nurses because the pumps offer a well-controlled infusion rate, accurate volume measurement, and an alarm system for monitoring the infusion.

Adolescent↗

Platelet counts in depressed patients treated with amitriptyline or paroxetine.

OBJECTIVE: To assess whether therapy with two widely used antidepressants influences platelet counts. SUBJECTS AND METHODS: In 90 patients hospitalized for treatment of a major depressive episode according to DSM-IV, platelet counts were performed after a 6 d antidepressant-free run-in period and again after 35 d of active standardized treatment with amitriptyline (n = 40) or paroxetine (n = 50). RESULTS: There was a trend for platelet counts to increase during treatment with amitriptyline (from 245.5 +/- 68.6 to 256.8 +/- 69 cells x 10(9) L(-1), P < 0.06); no change was observed during treatment with paroxetine (from 232.6 +/- 58.3 to 234.6 +/- 68.9 cells x 10(9) L(-1), n.s). CONCLUSION: Treatment with amitriptyline tends to be associated with elevated platelet counts. The cause for this increase is not known, but may be relevant in terms of patients' long-term thromboembolic risk.

Amitriptyline↗

Influence of charcoal haemoperfusion on platelet count in acute poisoning and during regular dialysis treatment.

Platelet count did not significantly decrease after charcoal haemoperfusion in patients with acute poisoning and significantly decreased during regular dialysis treatment. Adherent platelets and leucocytes were found on the surface of granules after haemoperfusion using a scanning electron microscope. Decreased platelet count returned to the original level at 48 to 72 hours after charcoal haemoperfusion.

Acute Disease↗

Increased platelet count as a screening test for distal splenorenal shunt patency.

Hypersplenism was not relieved by distal splenorenal shunting in 46 of 47 Japanese patients with nonalcoholic cirrhosis of the liver. However, the platelet count significantly increased by 40 percent of the preoperative value, whereas the increment in the white blood cell count was nil. Though the platelet count in 47 patients with a patent shunt did not significantly differ from that in another 7 patients with an occluded shunt, the rate of increase was significantly higher in those with patency than in those with early occlusion throughout the postoperative period and in those with late occlusion 6 months after operation. The increased rate of the platelet count can thus serve to screen patients for shunt patency.

Adult↗

Platelet count, anti-heparin/platelet factor 4 antibodies and tissue factor pathway inhibitor plasma antigen level in chronic dialysis.

We studied 50 chronic dialysis patients with end-stage renal disease. Mean platelet count was within normal limits. An inverse linear correlation was observed between pre-dialysis platelet count and serum creatinine (r=0.304, p=0.038). Dialysis caused a decrease in platelet count (216+/-80x10(9)/L, pre; 198+/-68, post; p=0.0001), and the higher the pre-dialysis platelet count, the greater the decrease (r=0.623, p=0.0001). Post-dialysis triglyceride decreased (1.67+/-1.27 mmol/L, pre; 1.23+/-0.96, post; p=0.0001). Tissue factor pathway inhibitor (TFPI) antigen plasma level was higher in uremic patients than in controls (114+/-42 ng/ml vs. 64+/-12, p=0.0001). TFPI increased 2.3 times following dialysis and such an increase was directly correlated with post-dialysis plasma heparin concentration (r=0.571, p=0.0002) and inversely correlated with post-dialysis triglyceride variation (r=0.407, p=0.005). Six of fifty patients (12%) had anti-heparin/platelet factor 4 antibodies (Hab), 3 IgG, and 3 IgM. Female sex and the use of cuprophane membranes were more frequent among Hab-positive patients (p=0.0001), while a lower percentage of them were on anti-aggregating drugs as compared to Hab-negative patients (p=0.002). Only one Hab-positive patient was slightly thrombocytopenic and none showed bleeding or thrombotic manifestations. Serum albumin and y globulin decreased following dialysis in Hab-positive patients, while the opposite was seen in those Hab-negative (-2.47+/-1.72 g/L, vs. 0.21+/-1.77, p=0.001 and -0.48+/-0.60 g/L vs. 0.64+/-0.97, p=0.007, respectively). In vivo factors other than Hab are involved in the development of heparin-induced thrombocytopenia. Besides a blunted immunological response, increased levels of TFPI, the use of anti-aggregating drugs, and the observed behavior of serum proteins might play a role in this regard.

Adult↗

Platelet counts and aggregation measures in the incidence of ischaemic heart disease (IHD).

Although studies in those who have already experienced clinical episodes of ischaemic heart disease (IHD) have suggested properties of platelets influencing recurrence, there is limited information on the value of platelet tests in predicting first episodes of IHD. One study has suggested that a raised platelet count and increased aggregability in response to adenosine diphosphate (ADP) may increase IHD incidence but the numbers of IHD events involved were small. The larger Northwick Park Heart Study (NPHS) included platelet count and both ADP and adrenaline-induced aggregation and this paper presents their associations with subsequent IHD. Platelet counts were performed in 1369 white NPHS men aged between 40 and 64 at recruitment, of whom 181 subsequently experienced a major episode of IHD over a follow-up period of 16.1 years. Platelet count was unrelated to the incidence of IHD. ADP-induced aggregation was performed in a random sample of 740 men in whom 66 IHD events occurred during the subsequent 10.1 years, aggregability being measured both as ED50, the ADP dose at which aggregation occurred at half its maximum velocity, and also as EMR, the maximum rate of aggregation achieved. Neither measurement showed any association with IHD incidence, nor did similar measurements in 460 men in whom adrenaline-induced aggregation was also carried out. There are at least three possible explanations for the lack of any association between the measures of aggregability used and IHD. First, the large within-person variability of platelet aggregation tests may make the demonstration of any associations difficult, though the study had reasonable power to show effects with ADP. Secondly, the tests used may not be a valid index of the contribution of platelet function to thrombosis and IHD. However, the clear effect of several personal and demographic influences associated with IHD on the tests used brings this explanation into question. Thirdly, the role of platelets in thrombogenesis may be determined mainly by plasma influences such as fibrinogen, rather than by intrinsic properties of platelets themselves. Platelet counts within the physiological range and the aggregation tests used in this and in some other studies are of no value as indices of the risk of first episodes of IHD.

Adult↗

Pulmonary embolism after cesarian section due to heparin-induced thrombocytopenia despite normal platelet count.

Heparin-induced thrombocytopenia (HIT) type II is typically characterized by a decrease in platelet count to values between 20 and 120 x 10 (9)/L or a platelet count fall of greater than 50%. We report on a patient who developed a HIT syndrome, thrombosis of the vena cava, and fulminant pulmonary embolism during heparin treatment after cesarean section, without a significant decrease in platelet count. Lepirudin anticoagulation and ecarin clotting time (ECT) monitoring were used successfully during cardiopulmonary bypass.

Adult↗

Two candidate genes for low platelet count identified in an Asian Indian kindred by genome-wide linkage analysis: glycoprotein IX and thrombopoietin.

A genome-wide linkage analysis of platelet count was carried out in a large Asian Indian kindred. Linkage analysis showed one marker (D3S1309) on chromosome 3q with a lod score of 3.26 and another (D3S1282) approximately 30 cM centromeric, with a lod score of 2.52. Multipoint analysis of chromosome 3q identified two peaks with maximum multipoint lod scores of 3.52 and 4.11 under markers D3S1309 and D3S1282, respectively. Two strong candidate genes for platelet variation were identified in the linked region; thrombopoietin (THPO) and glycoprotein IX (GPIX). Resequencing of four individuals revealed five single-nucleotide polymorphisms (SNPs) in THPO and one mutation in the transmembrane region of GPIX. Analysis of variance showed that the GPIX mutation and one THPO SNP accounted for 6 and 4% of the variation in platelet count, respectively. The THPO SNP lies in the 3' untranslated region of the gene and has not been previously reported. The G to A transition at nucleotide 653 resulted in an Ala 156 (GCC) to Thr (ACC) replacement in the GPIX protein. The GPIX mutation was recently identified in a Chinese patient with Bernard-Soulier syndrome (BSS), a rare recessive bleeding disorder characterized by thrombocytopenia and giant platelets. One copy of the GPIX mutation was found in 300 European individuals with platelet counts within the normal range. The results suggest that two QTLs on chromosome 3q influence platelet count variation in the Asian Indian kindred, with the GPIX transmembrane mutation and the 3' UTR SNP in THPO being strong candidates.

3' Untranslated Regions↗

The effect of high altitude on platelet counts, thrombopoietin and erythropoietin levels in young Bolivian airmen visiting the Andes.

Recognition of thrombosis as a complication of exposure to high altitude has stimulated interest in rheological changes resulting from hypobaric hypoxia. Previous studies of platelet counts at high altitude have yielded conflicting results and have not been studied in conjunction with potential mediating cytokines. We studied the effects of high-altitude exposure on platelet numbers, thrombopoietin (tpo) and erythropoietin (epo) levels in man. A group of 28 volunteers from the Bolivian Airforce stationed at Santa Cruz (600 m altitude) were studied 48 h and 1 week after their ascent to La Paz (3600 m). In addition 105 volunteers based at Santa Cruz for at least 1 year were compared with 175 age- and sex-matched residents at El Alto (4200 m). Platelet counts were measured immediately after sampling and serum samples assayed for tpo and epo. In the ascending group, mean platelet counts were 251 x 10(9), 367 x 10(9) and 398 x10 (9)/l at 600 m and following 48 h and 1 week at 3600 m respectively. Mean tpo levels were 132.5, 76 and 92 pg/ml with epo values of 2.98, 11.6 and 7.9 mIU/ml respectively. In the resident populations mean platelet counts were 271 x 10(9)/l in the low- and 471 x 10(9)/l in the high-altitude groups. Mean tpo and epo levels measured 69.3 pg/ml and 4.5 mIU/ml respectively at 600 m and 58.5 pg/ml and 5.1 mIU/ml at 4200 m. In conclusion we have demonstrated a significant and sustained elevation in platelet numbers within 48 h of ascent to high altitude. Our findings do not support a role for tpo as a mediator of the increased platelet count. However, these data do not discount epo as a potential candidate.

Adaptation, Physiological↗

Changes in antipyrine clearance and platelet count, but not conventional liver tests, correlate with fibrotic change in chronic hepatitis C: value for predicting fibrotic progression.

OBJECTIVE: We tested whether fibrotic progression in chronic hepatitis C could be predicted by liver tests, antipyrine clearance, or platelet count. METHODS: In 58 patients (6 untreated, 52 interferon-treated), a second liver biopsy was taken median 4.5 yr after first histologic diagnosis. We used receiver operating characteristic curves to determine whether changes in conventional liver tests, antipyrine clearance, or platelet count were predictive of altered hepatic fibrosis score. RESULTS: Apart from a weak association with change in ALT, conventional liver tests (albumin, bilirubin, prothrombin time) failed to correlate with changes (Delta) in hepatic fibrosis, but there were significant correlations between deltaantipyrine clearance or deltaplatelet count and deltafibrosis score (p < 0.01). As indicated by areas under the receiver operating characteristic curves, the diagnostic accuracy of deltaantipyrine clearance for fibrotic progression was 68%; for Deltaplatelet count it was 80%. With defined cut-off values (-0.05 ml/min/kg for deltaantipyrine clearance; -41 x 10(9)/L for deltaplatelet count), the negative predictive values for fibrotic progression were 85% with antipyrine clearance and 89% with platelet count. Corresponding positive predictive values were 48% and 91%, respectively. CONCLUSIONS: Changes in antipyrine clearance and platelet count are more sensitive than conventional tests for indicating fibrotic change in chronic hepatitis C. Both could be used to reliably identify those who do not have fibrotic progression, and platelet count also has a high positive predictive value for disease progression.

Adult↗