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Reticulated platelets predict platelet count recovery following chemotherapy.

BACKGROUND: A laboratory measure that predicted the timing of platelet recovery after chemotherapy could guide prophylactic platelet transfusion. Reticulated platelets (RPs) are the youngest circulating platelets; an increased percentage of RPs is diagnostic of increased marrow platelet production, such as seen with idiopathic thrombocytopenic purpura, whereas a low percentage of RPs with thrombocytopenia indicates marrow suppression. This study examined whether the percentage of RPs, in combination with a newly devised measurement of "stress thrombopoiesis," the RP maturation index (RP-MI), could predict platelet count recovery following chemotherapy-induced thrombocytopenia. STUDY DESIGN AND METHODS: Platelet count nadirs were retrospectively determined in 35 chemotherapy-induced thrombocytopenia patients; percentage of RPs and RP-MI values were assayed at the early nadir (no imminent platelet recovery) and the late nadir (imminent platelet recovery). The latter was defined by a platelet count increase of 20 x 10(9) per L or more in the subsequent 48 hours without platelet transfusion. RESULTS: Early in the nadir (when platelet recovery did not occur in the subsequent 48 h after sampling), a low RP-MI and a low percentage of RPs were found in 29 of 35 patients. Late in the nadir, when recovery was imminent, 27 of 30 evaluable patients had elevated percentages of RPs or RP-MI values; the mean time from sampling to an increase of 20 x 10(9) per L or more was 42 hours. The positive and negative predictive values of this assay were 82 and 91 percent, respectively. Furthermore, when thrombocytopenia was severe (platelet count < or = 20 x 10(9)/L), an elevated RP-MI and/or percentage of RPs correctly predicted imminent platelet count recovery in five of five patients. CONCLUSION: This noninvasive, rapid, whole-blood assay of stress thrombopoiesis provides reproducible indices for timing platelet recovery following chemotherapy and the potential to optimize the use of prophylactic platelet transfusions in chemotherapy patients.

Adult↗

Studies on reference intervals for platelet counts in three cities in China and one in Japan.

Hematological parameters including platelet counts, etc. were determined in 1,140 healthy subjects living in four cities: Suzhou (Jiangsu Province), Chengdu (Sichuan Province) and Harbin (Heilongjang Province) in China, and Kobe in Japan. Then, the reference intervals for platelet counts were calculated and compared. The reference interval for platelet count of subjects aged between 18 and 60 years was 60-259 x 10(9)/L in Suzhou and 52-202 x 10(9)L in Chengdu, and subjects with platelet counts of 100 x 10(9)/L or less accounted for about 30% of the subjects examined in these cities. The reference intervals in Harbin and Kobe were within the range of 150-350 x 10(9)/L, and no subject having a platelets count of 100 x 10(9)/L or less was detected. Mean platelet volume (MPV) determined concurrently was negatively correlated with platelet count, and the reference intervals for MPV in Chengdu and Suzhou were higher than those in Harbin and Kobe.

Adolescent↗

Prognostic importance of the platelet count 100 days post allogeneic bone marrow transplant.

We assessed the prognostic importance of the platelet count 100 days post transplant of 107 consecutive patients receiving ablative allogeneic bone marrow transplant (BMT) between 7/96 and 12/00 who survived at least 100 days. Diagnoses included AML (n=36), chronic myelogenous leukemia (n=27), NHL (n=14), ALL (n=16), MDS (n=9), aplastic anemia (n=3), and one Hodgkin's disease and myelofibrosis each. In total, 64% were in remission or in chronic phase or had aplastic anemia (good risk), and 36% had active disease at the time of transplant (bad risk). In all, 70% were matched sibling transplants and 30% were matched unrelated donor transplants. The mean follow-up for the patients remaining alive is 48 months. Survival was powerfully influenced by the 100-day platelet count: 4-year survival was 19% for patients with a platelet count <30 x 10(9)/l; 41% for patients with a platelet count of 30-50; and 72% for those with a platelet count >50 (P<0.001; log-rank test). In a multivariable analysis, the most powerful risk factors for mortality after allogeneic BMT were low 100-day platelet count (P<0.001) and bad risk disease (P=0.009). We conclude that the platelet count 100 days post transplant is a powerful predictor of overall survival.

Adolescent↗

How and why does the platelet count in postmortem blood change during the early postmortem interval?

We examined the changes in the early postmortem platelet count in postmortem blood and the reasons for these changes by counting the platelets, by performing in vitro hypostatic tests, by estimating the percentage of erythrocytes by volume in postmortem blood samples, by immunohistochemistry (anti-CD61, anti-fibrinogen), and by immunoelectron microscopy (anti-CD62, anti-CD63, anti-thrombospondin). The apparent initial increase in the platelet count in postmortem blood was found to be caused by hypostatic phenomena. The subsequent discontinuous decrease in the platelet count despite continuing hypostasis in the corpse can be explained in part by postmortem thrombolysis and the development of reversible platelet-platelet aggregates. The main point is, that changes in the postmortem blood environment cause potentially reversible adhesion of platelets to pre-adsorbed fibrinogen on erythrocytes. Thus the decrease in the number of platelets in postmortem blood is not attributable to postmortem clotting but to a decrease in the number of countable platelets in postmortem blood.

Adult↗

Platelet count in healthy full-term Nigerian neonates.

633 platelet counts are reported on 338 full-term healthy Nigerian babies aged 1 hour to 28 days. Platelet counts for the first week (207,000 +/- 72,000 cumm) are significantly lower (P less than .001) than in the subsequent 3 weeks (282,000 +/- 94,000 cumm). Platelet counts of 100,000-400,000/cumm during the first week and 100,000-450,000/cumm during the rest of the neonatal period include 95% of the respective age groups of Nigerian infants studied and these ranges can therefore be regarded as standard for healthy Nigerian neonates. Platelet counts in Nigerian neonates are essentially similar to those reported elsewhere but significantly higher than in Nigerian adults.

Blood Cell Count↗

Influence of tiapride on platelet counts in healthy volunteers and patients with movement disorders.

BACKGROUND: The selective D2 antagonist tiapride is administered in various movement disorders. Furthermore, there are indications that tiapride increases platelet counts. AIM: To characterize tiapride's potential to increase platelet counts in healthy subjects and patients with movement disorders. METHODS: In Part A, 10 healthy volunteers received tiapride (300 mg/day) for 21 days in a longitudinal, prospective, open trial. One hundred healthy subjects served as controls. Part B was a retrospective analysis of 15 patients with movement disorders on tiapride [Huntington's disease (n=6), Morbus Little (n=3), hyperkinetic syndromes of undetermined etiology (n=3), blepharospasm (n=1), cervical dystonia (n=1), perioral dyskinesia (n=1)] and 15 age- and sex-matched controls. RESULTS: Part A: Although serum prolactin levels increased by 526+/-14%, confirming good drug compliance, tiapride elicited only minor changes in platelet counts. Part B: Platelet counts correlated positively with the dose of tiapride (100-800 mg/day; r=.67; P=.007). Platelet counts were significantly higher in patients on tiapride compared to healthy age-matched controls (P<.001). Four patients responded to an increase in the tiapride dosage with an increase in platelet count by 97-173 cells/nl. CONCLUSION: Three weeks of treatment with tiapride (300 mg/day) is insufficient to elevate platelet counts to a clinically relevant extent in young healthy volunteers. However, in elderly patients with movement disorders tiapride treatment is associated with markedly increased platelet counts.

Administration, Oral↗

Influence of platelet count, acetylsalicylic acid, von Willebrand's disease, coagulopathies, and haematocrit on results obtained using a platelet function analyser in dogs.

The platelet function analyser PFA-100 aspirates blood in vitro from a sample reservoir in disposable test cartridges through a microscopic aperture cut into a biologically active membrane at the end of a capillary. In different cartridges the membrane is coated with collagen and adenosine diphosphate (ADP) or collagen and epinephrine (adrenaline) inducing a platelet plug and closure of the aperture. The closure time and total volume of blood flow through the capillary until closure of its aperture were measured. The correlation between platelet count in samples of thrombocytopenic dogs and results of the collagen/ADP cartridge (closure time: r(S)=-0.579; total volume: r(S)=-0.549) was closer than between platelet count and capillary bleeding time. No significant correlation was observed between platelet count and the results obtained with the collagen/epinephrine cartridge. In addition, a higher sensitivity was obtained for the collagen/ADP cartridge. Injection of acetylsalicylic acid into healthy dogs significantly increased closure time and total volume of both types of cartridges (P<0.01). Two dogs with von Willebrand's disease had abnormal values. In contrast, coagulopathies did not significantly influence the results of the platelet function analyser (P>0.05). Despite adequate sensitivity of measurements using the collagen/ADP cartridge to assess quantitative and qualitative platelet disorders in dogs, the influence of haematocrit (P<0.0001) will limit the clinical application of the analyser.

Animals↗

Pappenheimer bodies. An additional cause for a spurious platelet count.

A 67-year-old woman who had sideroblastic anemia had a spuriously elevated platelet count due primarily to Pappenheimer bodies. The platelet count on an electrooptical instrument was falsely elevated. The true platelet count was determined by phase microscopy using lysed whole blood and by the peripheral blood smear. There appear to have been no previous reports of falsely elevated platelet counts due to Pappenheimer bodies. Other causes of spuriously elevated platelet counts are reviewed. The reasons for the spurious counts are discussed.

Aged↗

Changes in platelet count and related parameters in SART-stressed mice and the action of administered neurotropin.

In order to hematologically characterize SART-stressed (repeated cold-stressed) animals, which are regarded as model animals of clinical dysautonomia, general hematological analyses were performed in mice subjected to various types of stress. SART-stressed mice showed significant increases in erythrocyte count, hemoglobin, hematocrit and specific gravity of whole blood, no change in leukocyte count and a marked decrease in platelet count. Among the above changes, the decreased platelet count was particularly characteristic of SART-stressed mice. Splenectomy failed to inhibit the SART stress-induced thrombocytopenia. Bone marrow megakaryocyte counts increased following the stress. The bleeding time of SART-stressed mice was more than double that of normal mice. Consecutive administrations of Neurotropin, a sedative analgesic, completely blocked the alterations in platelet count, megakaryocyte count and bleeding time in SART-stressed mice without producing any effect in unstressed mice. From the present results, it is suggested that SART-stressed mice may be characterized by thrombocytopenia, which is not attributable to enhanced function of the spleen or suppressed platelet production in the bone marrow. Moreover, Neurotropin appears to be effective for moderating SART stress.

Alprazolam↗

Moderate and extreme haemodilution in open-heart surgery. Blood requirements, bleeding and platelet counts.

Requirements of donor blood, bleeding and platelet counts were investigated during moderate and extreme haemodilution in patients undergoing aortic valve replecement. A preliminary study of 60 patients, divided in two groups of 30 patients each, was first made. A moderate haemodilution was used in one group and an extreme haemodilution with the aid of autologous transfusion was utilized in the other. As the results were interesting and encouraging, a randomized study was performed. Thirty patients, divided in two groups of 15 patients each, were investigated. The degree of dilution was essentially similar to that of the corresponding moderate and extreme haemodilution groups in the preliminary study. An average reduction of 71% in the requirement of donor blood and of 47% in postoperative chest tube drainage was found in the patients in the extreme dilution group. The circulating platelet counts fell less during and after the operation in this group than in the moderately diluted patients. After adjustment for the dilution, the platelet counts fell to about 60% in the moderate dilution group during the perfusion, but rose to about 130% in the extremely diluted patients. These findings are discussed.

Adult↗

Evaluation of a semi-automated platelet-counting system.

Coulter Electronics Ltd have produced a semi-automated platelet-counting system. Platelet-rich plasma may be obtained either by tube sedimentation or by means of the Thrombo-fuge, the latter being an instrument designed to produce accelerated sedimentation. The instrument is linear over the entire range of platelet counts, and machine reproducibility is good. Comparison of machine-rated with visual counts satisfied statistical evaluation. The technique can be handled by one operator and platelet counts can be achieved at the rate of 30 per hour by both methods although individual counts on the Thrombo-fuge may be obtained in approximately one-quarter of the time required for tube sedimentation. The throughput using the Thrombo-fuge could certainly be doubled were two sample plates supplied. Few problems were encountered during the evaluation and most could be avoided by meticulous technique. Visual counts must be performed when the sample haematocrit is greater than 50%-Discrepant counts have been obtained in patients with white cell counts exceeding 50 X 10(9)/1 and in patients with giant platelets. ESR elevation for any reason does not lead to serious discrepancy in results. The incidence of platelet clumping due to the presence of platelet agglutinins and of microclot formation due to inadequate mixing is probably much higher than is commonly thought, and certainly peripheral blood film scrutiny should never be omitted in patients with low counts. Careful examination of peripheral blood films must be combined with instrument counting for some time lest further causes of discrepant counting emerge.

Blood Platelets↗

Extent of hepatectomy on splenic hypertrophy and platelet count in live liver donors.

The extent of donor hepatectomy may affect splenic hypertrophy and platelet count. The subjects were 50 live liver donors. The ratio of the graft weight to total liver volume (GW/TLV) and the splenic hypertrophy ratio, expressed as the splenic volume one month after surgery divided by that before surgery, were calculated. The platelet count one month after surgery was divided by that before surgery to determine the rate of the platelet count decrease. The correlation of GW/TLV to the splenic hypertrophy ratio and the rate of the platelet count decrease were examined. The median (range) GW/TLV was 54 (28-71)%. The splenic hypertrophy ratio and the rate of the platelet count decrease was 133 (99-191)% and 92 (71-129)%, respectively. GW/TLV positively correlated with the splenic hypertrophy ratio (Spearman's correlation coefficient (r(s)) = 0.448, p = 0.001), and negatively correlated with the rate of the platelet count decrease (r(s) = -0.471, p < 0.001). Multivariate analysis revealed that GW/TLV influenced the splenic hypertrophy ratio [adjusted odds ratio (OR), 12.0; 95% confidence interval (CI), 1.32-9.04; p = 0.01] and the ratio of the platelet count decrease (adjusted OR, 11.6; 95% CI, 1.40-8.33; p = 0.01). Larger graft procurement might place living liver donors at higher risk for post-operative thrombocytopenia.

Body Weight↗

Platelet count at term pregnancy: a reappraisal of the threshold.

OBJECTIVE: To assess the safety of a new platelet count threshold for the definition of maternal thrombocytopenia late in pregnancy. METHODS: A platelet count was performed in 6770 pregnant women late in pregnancy and in 6103 of their newborns as well as in a control group of 287 age-matched nonpregnant healthy women. RESULTS: The prevalence of maternal thrombocytopenia (platelet count less than 150 x 10(9)/L) was 11.6%. The mean platelet counts (248 compared with 213 x 10(9)/L) and 2.5th percentile (164 compared with 116 x 10(9)/L) were significantly higher in healthy nonpregnant women than in pregnant women. Among thrombocytopenic pregnant women, 621 (79%) had platelet counts between 116 and 149 x 10(9)/L; none (0%; 95% confidence interval 0, 0.6) had complications related to thrombocytopenia, and none of their newborns had severe thrombocytopenia (platelet count less than 20 x 10(9)/L). CONCLUSION: In healthy pregnant women, a platelet count over 115 x 10(9)/L late in pregnancy does not require further investigation during pregnancy and may be considered a safe threshold.

Adolescent↗

A second-generation blood substitute (Perfluorodichlorooctane emulsion) generates spurious elevations in platelet counts from automated hematology analyzers.

UNLABELLED: Perfluorocarbon emulsions (PFEs) appear as platelets in automated cell counters, which may affect samples from thrombocytopenic patients (less than 100,000/microL). Therefore, we mixed clinically relevant concentrations of perfluorodichlorooctane (Oxyfluor(R); Hemagen, Inc., St. Louis, MO) in vitro with whole blood samples ranging from 0 to 150,000 platelets/microL and compared a new counter that uses optical platelet recognition (Abbott CellDyn 3200; Santa Clara, CA) with conventional electroimpedance-based counters (Abbott CellDyn 3500 and CellDyn 1700). We found that emulsion particles appear as small-sized platelets either in diluent or in blood. The emulsion results in a reproducible overestimate of the platelet counts, of greater importance as PFE concentration increases, and as the actual platelet count of the blood samples decreases. The new optical technology yields smaller overestimates but, even at low PFE concentrations, gives an unacceptable relative error at platelet counts near the transfusion thresholds recommended by the American Society of Anesthesiologists guidelines for blood component therapy. Unexpected interference in the leukocyte and erythrocyte channels is also reported. Experimental limitations preclude extrapolation of these findings to other automated cell counters, because differences in technology or software may affect their capacity to separate PFE particles from platelets. IMPLICATIONS: Perfluorocarbons are being investigated under conditions in which thrombocytopenia is likely to occur. In this in vitro study, we demonstrate significant overestimates in platelet counts from automated cell counters at clinically relevant perfluorocarbon concentrations in thrombocytopenic blood samples.

Blood Substitutes↗

Initial fetal platelet counts predict the response to intravenous gammaglobulin therapy in fetuses that are affected by PLA1 incompatibility.

OBJECTIVE: Fetal alloimmune thrombocytopenia is the result of maternal fetal platelet antigen incompatibility; intracranial hemorrhage is its most serious complication. Our previous studies have demonstrated an inability to accurately predict fetal platelet counts in this disorder. The goal of the present investigation was to identify factors that would predict the response of the fetal platelet count to therapy so that use of fetal blood sampling could be minimized. STUDY DESIGN: Patients who were eligible for the study were all those who (1) had alloimmune thrombocytopenia secondary to Pl(A1) (HPA-1a, Zw(A)) platelet antigen incompatibility, (2) were treated with maternally administered intravenous immunoglobulin at 1 g/kg of body weight per week, with or without low dose steroids, and (3) had percutaneous fetal blood sampling before the initiation of therapy (first fetal blood sampling) and again 3 to 7 weeks afterwards (second fetal blood sampling). RESULTS: In this retrospective review, 74 patients who were affected by alloimmune thrombocytopenia had a median platelet count of 21,000 per microliter at the first fetal blood sampling and 47,000 per microliter at the second fetal blood sampling, with a median increase in platelet count of 24,000 per microliter. Response to treatment was defined as either (1) an improvement in platelet count (the second fetal blood sampling greater than the first fetal blood sampling, and second fetal blood sampling > 20,000 per microliter) or (2) a minimal decline in platelet count (the first fetal blood sampling > or = 40,000 per microliter and the difference between the first and second fetal blood sampling < or = 10,000 per microliter). The first fetal blood sampling had prognostic value for the second fetal blood sampling (P = .0001), although the previous sibling birth platelet count and history of sibling intracranial hemorrhage did not predict the platelet count at the first or second fetal blood sampling or the change in platelet count between the samplings. When the patients were segregated to first fetal blood sampling of > 20,000 per microliter versus < or = 20,000 per microliter, the response rates for the 2 groups were 89% (33/37 patients) versus 51% (19/37 patients; P = .001). CONCLUSION: In fetal alloimmune thrombocytopenia secondary to Pl(A1) platelet antigen incompatibility, fetuses with platelet counts > 20,000 per microliter at the initiation of therapy were predicted to maintain their platelet count at the second fetal blood sampling at > 20,000 per microliter. The characteristics of the previous sibling, as previously reported, did not predict the initial fetal blood sampling, the second fetal blood sampling, or the response to treatment.

Adult↗

Platelet counts in stored donor blood.

Platelets were counted in eight units each of one- and three-day-old blood. Counts were done both before and after the blood had passed through a standard 170 micron filter. In the one-day-old blood, platelet counts were within the normal range. The mean count was 237,000 platelets/microlitre. Platelet counts on three-day-old blood were lower, but generally still within the normal range. The mean count was 183,000/microlitre. Only a few platelets were retained by the filter in the transfusion set; about 90% of platelets passed the filter in both the one- and three-day-old blood. It appears that whole blood, anticoagulated with citrate/phosphate/dextrose (CPD), and stored under Australian blood bank conditions retains platelets in sufficient numbers for at least the first three days to be clinically significant. However, it remains to be determined whether satisfactory platelet activity can be expected during this time.

Blood Preservation↗

Low platelet count and elevated serum thrombopoietin after severe trauma.

Platelet count is regularly low in patients after multiple trauma, mainly due to blood loss and dilution. Thrombopoietin (TPO) is the main regulator of the circulating platelet mass. Under several clinical conditions an inverse correlation between TPO and the circulating platelet mass was reported. Since platelets bind and internalize TPO, a platelet-dependent regulation of TPO was suggested. Thus, acute blood loss should be accompanied by elevated TPO. We measured serum TPO, platelets, interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in 17 multiple traumatized victims. Blood was collected within 12 h after trauma as well as in the morning of days 2, 4, 6 and 9 after admission at the intensive care unit. Platelet count was low at admission and remained low until day 4. Thereafter platelets increased until day 9. TPO nearly doubled within the first 2 d, reaching its maximum on day 6. IL-6 was initially very high and steadily decreased until day 9. VEGF increased 3-fold during the 9 d. Statistically significant correlations of TPO were found with platelets and IL-6, but not with VEGF. In multiple traumatized patients low platelet count is followed by a rapid increase in serum TPO. This fits into the concept of a feedback regulation between circulating TPO and platelet mass.

Adult↗

Patterns of platelet response in idiopathic TTP/HUS: frequency of declining platelet counts with plasma exchange and the recognition and significance of a pseudo refractory state.

For thrombotic thrombocytopenic purpura (TTP), daily plasma exchange (TPE) is typically discontinued when the platelet count normalizes (>150 x 10(9)/L). We observed a decline in platelet count during TPE and in patients who appeared pseudo-refractory because of a platelet count plateau (100-150 10(9)/L range). In the present study, we evaluated platelet count trends in TTP patients. Retrospective review of TTP patients from 01/1999 to 12/2004 was completed. Patients were categorized based on platelet count trends: Group I, counts rose then decreased to levels <100 x 10(9)/L; Group II, counts declined following TPE initiation; Group III, counts rose continuously; Group IV, counts decreased after the count was >100 x 10(9)/L. Additionally, we identified pseudo-refractory patients caused by a platelet count plateau (>100 x 10(9)/L but <150 x 10(9)/L). We identified 60 TTP patients. Within Group I (17 patients/17 series/19.1% of total), the mean decrease in platelet count was 67.3% +/- 22.1% following initial rise. Within Group II (24 patients/25 series/28.1% of total), the mean decrease was 28% +/- 5.3% following presentation. Group III included 31 patients/39 series (43.8% of the total). Within Group IV (seven patients/eight series/9.0% of total), the mean decrease was 17.4% +/- 12.6% following a sustained rise >100 x 10(9)/L. With a declining platelet count and daily TPE, it is generally sufficient to stay the course and the decline will reverse. Our limited experience with pseudo-refractory patients supports discontinuing TPE when counts plateau between 100 and 150 x 10(9)/L when a therapy goal is a platelet count of 150 x 10(9)/L. Recognition of this pseudo-refractory state can minimize the risks of prolonged TPE and the risks of adjunct interventions.

Adolescent↗