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1.  Hypoxia as a Predisposing Factor for the Development of Early Onset Neonatal Thrombocytopenia 
Journal of Clinical Neonatology  2012;1(3):131-134.
Background:
Thrombocytopenia in hypoxic neonates admitted in NICU is a morbid condition encountered very commonly. Early-onset thrombocytopenia (<72 h) is most commonly associated with fetomaternal conditions complicated by placental insufficiency and/or fetal hypoxia. Chronic intrauterine hypoxia is the most frequent cause of early-onset thrombocytopenia in preterm neonates.
Aims:
In this study incidence and clinical impact of early thrombocytopenia in hypoxic neonates was investigated.
Setting and Design:
Neonatal intensive care unit of a tertiary level hospital attached to a medical college in Central India. A cross-sectional, observational hospital based study in hypoxic neonates for development of thrombocytopenia.
Materials and Methods:
603 hypoxic newborns were evaluated for development of thrombocytopenia. 155 (25.07%) developed thrombocytopenia and were the cases. Non thrombocytopenic babies 448 (74.29%) served as controls. The two groups were compared for birth weight, sex ratio, gestational age, severity of asphyxia, platelet counts and mortality rate.
Statistical Analysis:
Descriptive statistics of continuous variable were expressed in mean and SD. P value less than or equal to 0.05 were statistically significant.
Results and Conclusions:
We found thrombocytopenia to be associated with male gender, prematurity and low birth weight. Most babies had mild to moderate thrombocytopenia. Mortality was higher in preterm thrombocytopenic babies as compared to term. We suggest screening for thrombocytopenia in all asphyxiated newborns, as hypoxia can lead to neonatal thrombocytopenia.
doi:10.4103/2249-4847.101693
PMCID: PMC3762028  PMID: 24027708
Neonate; birth asphyxia; hypoxia; thrombocytopenia; platelet count
2.  Platelet counts and outcome in the pediatric intensive care unit 
Objectives:
Thrombocytopenia is commonly observed in critically ill patients. This study was undertaken to evaluate the variation in platelet counts and the risk factors associated with thrombocytopenia and mortality in pediatric intensive care patients. In addition, prognostic value of platelet counts for outcome in pediatric intensive care unit was studied.
Study Design:
Prospective, observational cohort analysis.
Setting:
8- bedded pediatric intensive care unit of a tertiary care teaching hospital.
Patients:
All consecutively admitted patients (n=138) staying in the pediatric intensive care unit (PICU) for at least 48h over a 7 months period were studied.
Measurements and Main Results:
Thrombocytopenia was defined as platelet counts <150.0/nL. Median 1st day Pediatric Risk of Mortality Score (PRISM) was 5 (range 0-30) and median ICU stay was 4 days (range 2-98 days). Twenty five percent patients had at least one episode of thrombocytopenia during the stay. Twenty percent of these patients had thrombocytopenia on admission and rest (80%) developed it during the PICU stay. Seventy one percent (19) of the patients developed thrombocytopenia by fourth day of admission. Patients with PICU acquired thrombocytopenia had statistically significant lower baseline, nadir and 4th day platelet counts and a significantly higher drop in platelet counts (56% vs. 6% P<0.001) as compared to non thrombocytopenic patients. PRISM score, long PICU stay, sepsis, coagulopathy, and creatinine levels were significantly associated with occurrence of thrombocytopenia. Patients with thrombocytopenia had higher probability of bleeding (34% vs. 15%, P=0.01). Higher platelet counts on admission were associated with significantly reduced risk of thrombocytopenia (P=0.00) Baseline, nadir and day-4 platelet counts, presence of thrombocytopenia on admission, sepsis, coagulopathy and a higher mean PRISM score on univariate analysis were significantly associated with mortality. Leucopenia or leucocytosis, thrombocytopenia and coagulopathy were found to significantly affect outcome. Drop in platelet counts was found to have slightly higher discriminative value for mortality prediction than PRISM on the ROC curve. The survivors had higher platelet counts throughout the PICU stay and after an initial fall in platelet counts in the PICU showed a significantly higher rise in the platelet counts in the following days than the non-survivors.
Conclusions:
Thrombocytopenia is common in PICU. Patients requiring cardiopulmonary resuscitation or with circulatory shock, coagulopathy, sepsis and with more severe disease have higher risk of developing thrombocytopenia. Thrombocytopenic patients have a higher risk of bleeding. Drop in platelet counts >27% and thrombocytopenia were independently related to mortality. Serial measurements of platelet counts are better predictors of pediatric intensive care outcome than one-time values. Any drop in platelet counts even without thrombocytopenia needs an urgent and extensive evaluation.
doi:10.4103/0972-5229.43678
PMCID: PMC2738316  PMID: 19742257
Coagulopathy; mortality; pediatric intensive care; platelets; prognosis; thrombocytopenia
3.  Thrombocytopenia and Associated Factors in Neonates Admitted to NICU during Years 2010_2011 
Background
Thrombocytopenia is the most common hematological abnormality which is encountered in the neonatal intensive care unit (NICU). The incidence in neonates varies greatly, depending upon the population studies. According to the frequency of thrombocytopenia and its complications and because of lack of such research in Iran, this study was performed on neonates admitted to Shahid Sadughi NICU during years 2011-2012.
Materials and Methods
In a retrospective study, 350 neonates who were admitted to NICU were enrolled in the study. They were categorized to three groups regarding platelet count: mild, moderate and severe thrombocytopenia. Incidence of thrombocytopenia was determined and contribution of variables such as sex, gestational age, intrauterine growth retardation, asphyxia, sepsis, necrotizing enterocolitis, blood group, placental insufficiency in Gestational Diabetes Mellitus (GDM) and hypertension (HTN) were analyzed.
Results
Neonatal thrombocytopenia was found in 100(28.5%) of 350 subjects, consisted of 75.3% early onset and 24.7% late onset, which most of them (96.5%) had mild and moderate thrombocytopenia, and just 3.5% had developed severe thrombocytopenia. Thrombocytopenia was associated with sepsis, intrauterine growth retardation sepsis, asphyxia, GDM, maternal hypertension and prematurity. There was no relation between occurrence of thrombocytopenia and gender.
Conclusion
 The incidence of neonatal thrombocytopenia was 28.5 %. Significant maternal risk factors that lead to thrombocytopenia were HTN and preeclampsia, while risk factors of neonates were asphyxia, sepsis and Intera Uterus Growth Retardation.
PMCID: PMC3915438  PMID: 24575265
Thrombocytopenia; Intensive Care Units; Neonatal; Incidence
4.  Effects of in-vitro adult platelet transfusions on neonatal hemostasis 
Background
Thrombocytopenia is frequent among neonates, and 20-25% of affected infants are treated with platelet transfusions. These are frequently given for mild thrombocytopenia (platelets 50-100×109/L), largely due to the known hyporeactivity of neonatal platelets. In tests of primary hemostasis, however, neonates have shorter bleeding and closure times (CTs) than adults. This has been attributed to their higher hematocrits, higher von Willebrand factor (VWF) concentrations, and predominance of longer VWF polymers.
Objective
To determine whether the “transfusion” of adult (relatively hyper-reactive) platelets into neonatal blood results in a hypercoagulable profile.
Methods
Cord blood (CB) and adult peripheral blood (PB) were separated (using a modified buffy-coat method) to generate miniaturized platelet concentrates (PCs) and thrombocytopenic blood. PB- and CB-derived PCs (n=7 per group) were then “transfused” in-vitro into thrombocytopenic CB and PB. The effects of autologous vs. allogeneic (developmentally mismatched) “transfusions” were evaluated using whole blood aggregometry, platelet function analyzer (PFA-100), and thromboelastography (TEG).
Results
Adult platelets aggregated significantly better than neonatal platelets in response to TRAP, ADP and collagen, regardless of the blood into which they were transfused. The “transfusion” of adult platelets into thrombocytopenic CB resulted in shorter CTs-Epi (PFA-100) and higher clot strength and firmness (TEG), compared to “transfusion” of neonatal autologous platelets.
Conclusions
In vitro “transfusion” of adult platelets into neonatal blood results in shorter CTs than “transfusion” with neonatal platelets. Our findings should raise awareness of the differences between the neonatal and adult hemostatic system and the potential “developmental mismatch” associated with platelet transfusions on neonatal hemostasis.
doi:10.1111/j.1538-7836.2011.04233.x
PMCID: PMC3130591  PMID: 21320282
5.  Pseudo (Platelet-type) von Willebrand disease in pregnancy: a case report 
Background
Pseudo (platelet-type)-von Willebrand disease is a rare autosomal dominant bleeding disorder caused by an abnormal function of the glycoprotein lb protein; the receptor for von Willebrand factor. This leads to an increased removal of VWF multimers from the circulation as well as platelets and this results in a bleeding diathesis. Worldwide, less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD).
Case presentation
We describe the management of platelet type von Willebrand disease in pregnancy of a 26 year old Caucasian primigravida. The initial diagnosis was made earlier following a significant haemorrhage post tonsillectomy several years prior to pregnancy. The patient was managed under a multidisciplinary team which included obstetricians, haematologists, anaesthetists and neonatologists. Care plans were made for the ante- natal, intra-partum and post-partum periods in partnership with the patient. The patient’s platelet count levels dropped significantly during the antenatal period. This necessitated the active exclusion of other causes of thrombocytopenia in pregnancy. A vaginal delivery was desired and plans were made for induction of labour at 38 weeks of gestation with platelet cover in view of the progressive fall of the platelet count. The patient however went into spontaneous labour on the day of induction. She was transfused two units of platelets before delivery. She had an unassisted vaginal delivery of a healthy baby. The successful antenatal counselling has encouraged the diagnosis of the same condition in her mother and sister. We found this to be a particularly interesting case as well as challenging to manage due to its rarity. Psuedo von Willebrand disease in pregnancy can be confused with a number of other differential diagnoses, such as gestational thrombocutopenia, idiopathatic thrombocytopenia, thrombotic thrombocytopenic purpura and pre-eclampsia; all need consideration during investigations even in a case such as this where the diagnosis of platelet type von Willebrand disease was known before pregnancy.
Conclusion
Management of pseudo von Willebrand disease in pregnancy involves the co-operation of multidisciplinary teams, regular monitoring of platelet levels and factor VIII and replacement as appropriate. This case report highlights this rare condition and the need to exclude all the other differential diagnoses of thrombocytopenia in pregnant women with thrombocytopenia.
doi:10.1186/1471-2393-13-16
PMCID: PMC3558368  PMID: 23327637
Von Willebrand; Platelet type; Thrombocytopenia; Pregnancy
6.  Pregnancy outcomes in women with idiopathic thrombocytopenic purpura 
Background: Idiopathic thrombocytopenic purpura (ITP) is a disease that commonly affects women of reproductive age and is associated with maternal and fetal complications.
Objective: The aim of the present study was to report the perinatal outcome in pregnant women with ITP.
Materials and Methods: Twenty one pregnant women with ITP admitted in a teaching hospital in Tehran, from October 2008 to February 2010, were enrolled in this prospective historical cohort study; course and perinatal outcome of pregnancies were studied.
Results: Seven (33.3%) cases had been diagnosed before pregnancy, while the other fourteen (66.7%) were diagnosed during pregnancy. During hospitalization, thirteen (62%) patients required treatment, eight (61.5%) of them with steroids, two (15.3%) received intravenous immunoglobulin (IVIG), and three (23%) were treated with steroids and IVIG. Three babies were delivered vaginally (14.3%), seventeen (81%) through cesarean section and one patient aborted her fetus. Nine mothers (42.9%) had platelet counts <50000/ml at the time of delivery; but postpartum hemorrhage occurred in 4 (19%) women and one women received platelet transfusion during cesarean section. Six (28.6%) women developed gestational diabetes. Pregnancy was complicated by preeclampsia in one woman and by abruptio placenta in another. One pregnancy terminated in intrauterine fetal death. Seventeen infants (89.5%) had normal platelet counts, and two (10.5%) had moderate thrombocytopenia. No infant showed signs of hemorrhage, but 2 neonates (10.5%) were diagnosed with intrauterine growth restriction.
Conclusion: Rate of gestational diabetes in pregnant women with ITP is higher than the general population. Rate of gestinational diabetes is 3-5% and postpartum hemorrhage is 5-7% in general. Postpartum hemorrhage is common in these women. Severe thrombocytopenia and bleeding in the newborns are uncommon.
PMCID: PMC4169689  PMID: 25246917
Pregnancy outcomes; Idiopathic thrombocytopenic purpura; Neonatal outcome
7.  Neonatal outcome in alloimmune thrombocytopenia after maternal treatment with intravenous immunoglobulin 
Blood Transfusion  2015;13(1):66-71.
Background
Weekly maternal intravenous immunoglobulin (IVIG) is the cornerstone of antenatal treatment of foetal and neonatal alloimmune thrombocytopenia (FNAIT). The aim of this study was to describe the neonatal outcome and management in neonates with FNAIT treated antenatally with IVIG.
Materials and methods
All neonates treated antenatally and delivered at our centre between 2006 and 2012 were included in the study. We assessed the neonatal outcome and management, including the occurrence of intracranial haemorrhage, platelet count at birth and need for postnatal platelet transfusions or postnatal IVIG treatment.
Results
A total of 22 neonates were included of whom 12 (55%) had severe thrombocytopenia at birth (platelet count ≤50×109/L). Most neonates (67%, 8/12) with severe thrombocytopenia received a platelet transfusion after birth. None of the neonates required postnatal treatment with IVIG. Three neonates had petechiae and haematomas, without clinical consequences. One foetus suffered from intracranial haemorrhage, which was detected just before the planned start of antenatal IVIG at 28 weeks’ gestation.
Discussion
Our results suggest that antenatal maternal IVIG and, if necessary, postnatal matched platelet transfusions, are effective and safe for the treatment of FNAIT.
doi:10.2450/2014.0309-13
PMCID: PMC4317092  PMID: 24960663
alloimmune thrombocytopenia; neonatal; intravenous immunoglobulin; intracranial haemorrhage
8.  Thrombocytopenia in leptospirosis and role of platelet transfusion 
Aim:
The study was designed to find out the incidence of thrombocytopenia in leptospirosis and to correlate thrombocytopenia with other parameters like renal failure, hepatic failure and bleeding manifestation like adult respiratory distress syndrome and to assess the role of platelet transfusion.
Materials and Methods:
50 cases of leptospirosis during the month of July and August 2005 were retrospectively analyzed. Criteria for selection were Lepto Tek Dri - dot test positive cases of the clinically suspected cases of Leptospirosis. Degree of thrombocytopenia was categorized as severe, moderate and mild. Presence of thrombocytopenia was clinically correlated with parameters like renal dysfunction, hepatic dysfunction and hemorrhagic manifestations (mainly ARDS). Role of platelet transfusion was assessed with reference to presence and degree of thrombcytopenia and hemorrhagic manifestations.
Results:
Out of total 50 patients 26 were male and 24 were females. Major bleeding manifestation in the form of ARDS was seen in 15 (30%) of patients. 28 (56%) patients had thrombocytopenia and 22 (44%) patients had normal platelet counts. Total number of patients with renal dysfunction was 24 (48%). Only four (18.18%) patients with normal platelet counts had renal dysfunction while 20 (71.42%) patients with thrombocytopenia had renal dysfunction. Only two (9.09%) patients with normal platelet counts and 48 (46.42%) patients with thrombocytopenia had hepatorenal dysfunction. Total number of patients with ARDS was 15 (30%). Of these two (13.33%) had normal platelet count while 13 (86.6%) patients were thrombocytopenic. Total 47 units of platelets were transfused to 12 patients in our study. Of these seven patients with severe thrombocytopenia required total 28 units, two patients with moderate thrombocytopenia required total seven units and patients with mild thrombocytopenia were transfused total 12 units of platelets.
Conclusion:
It is important to anticipate and recognize thrombocytopenia early in the course of leptospirosis so that appropriate steps can be taken to prevent it and to treat it with platelet transfusion when it develops
doi:10.4103/0973-6247.33447
PMCID: PMC3168120  PMID: 21938233
ARDS; hepatic dysfunction; leptospirosis; platelet transfusion; renal dysfunction; thrombocytopenia
9.  NEW INSIGHTS INTO THE MECHANISMS OF NON-IMMUNE THROMBOCYTOPENIA IN NEONATES 
Seminars in perinatology  2009;33(1):43-51.
Thrombocytopenia affects up to 35% of all patients admitted to the neonatal intensive care unit (NICU). The causes of thrombocytopenia in neonates are very diverse, and include immune and non-immune disorders. Most cases of thrombocytopenia encountered in the NICU are non-immune, and these will constitute the focus of this review. Specifically, we will first discuss the biological differences between neonatal and adult megakaryocytopoiesis, which contribute to explain the vulnerability of neonates to develop thrombocytopenia. Next, we will review new diagnostic tools that have allowed for a better evaluation of platelet production in neonates, without having to obtain a bone marrow sample. Finally, we will summarize our current understanding of the mechanisms underlying the thrombocytopenia in several common neonatal conditions, such as chronic intrauterine hypoxia, sepsis and necrotizing enterocolitis (NEC), and viral infections. A better understanding of the mechanisms underlying these varieties of thrombocytopenia is critical to develop disease-specific treatment protocols, and to begin to entertain the possibility of using novel thrombopoietic growth factors to treat selected neonates with severe thrombocytopenia.
doi:10.1053/j.semperi.2008.10.008
PMCID: PMC2674325  PMID: 19167581
10.  NEONATAL THROMBOCYTOPENIA AND MEGAKARYOCYTOPOIESIS 
Seminars in hematology  2010;47(3):281-288.
Thrombocytopenia is common among sick neonates, affecting 20–35% of all patients admitted to the neonatal intensive care unit (NICU). While most cases of neonatal thrombocytopenia are mild or moderate and resolve within 7–14 days with appropriate therapy, 2.5–5% of NICU patients develop severe thrombocytopenia, sometimes lasting for several weeks and requiring >20 platelet transfusions. The availability of thrombopoietic agents offers the possibility of decreasing the number of platelet transfusions and potentially improving the outcomes of these infants. Adding thrombopoietin (TPO) mimetics to the therapeutic armamentarium of neonatologists, however, will require careful attention to the substantial developmental differences between neonates and adults in the process of megakaryocytopoiesis and in their responses to TPO. Taken together, the available data suggest that TPO mimetics will stimulate platelet production in neonates, but might do so through different mechanisms and at different doses than those established for adults. In addition, the specific groups of thrombocytopenic neonates most likely to benefit from therapy with TPO mimetics need to be defined, and the potential non-hematological effects of these agents on the developing organism need to be considered. This review summarizes our current understanding of neonatal megakaryocytopoiesis, and examines in detail the developmental factors relevant to the potential use of TPO mimetics in neonates.
doi:10.1053/j.seminhematol.2010.04.002
PMCID: PMC2934854  PMID: 20620440
11.  Unfurling the Rationale Use of Platelet Transfusion in Dengue Fever 
Dengue fever and dengue haemorrhagic fever have emerged as a global public health problem in recent decades. The practice of platelet transfusion has been adapted into the standard clinical practice in management of hospitalized dengue patients. The exact indications and situations in which platelet have to be transfused may vary greatly. Blood components especially platelet concentrates due to their short shelf life are frequently in limited supply. Hence, appropriate use of blood is required to ensure the availability of blood for patients in whom it is really indicated, as well as to avoid unnecessary exposure of the patients to the risk of transfusion reactions and transmission of blood borne infection. The present study was conducted to evaluate the appropriateness of platelet transfusion done in dengue patients with thrombocytopenia. The present study was conducted on 343 serologically confirmed dengue patients admitted at JSS University Hospital between 1st January and 30th August 2009. Clinical data, platelet count and platelet requirements were analyzed. Among the 343 serologically confirmed cases, the prevalence of thrombocytopenia (platelet count < 100,000/cumm) was 64.72% (222 patients) and bleeding manifestations were recorded in 6.12% (21 patients). 71 (20.7%) patients of dengue cases received platelet transfusion. Among them 34 (47.89%) patients had a platelet count <20,000/cumm, 28 patients (39.44%) had platelet counts in the range of 21–40,000/cumm while the remaining 9 (12.67%) patients had platelet count between 41–100,000/cumm. Out of 37 patients with a platelet count >20,000/cumm 11 patients had haemorrhagic manifestations such as petechiae, gum bleeding, epistaxis etc., which necessitates the use of platelet transfusion. However, the remaining 26 patients with platelet count >20,000/cumm and with no haemorrhagic manifestations received inappropriate platelet transfusion. Transfusion of 36.62% of platelet concentrate was inappropriate. The study emphasizes the need for development of specific guidelines for transfusion of blood components, constant interaction and co-ordination amongst clinicians and transfusion centre for implementation of these guidelines and a regular medical audit to review the optimal utilization of blood components.
doi:10.1007/s12288-011-0059-1
PMCID: PMC3136676  PMID: 22654295
Dengue; Haemorrhagic fever; Platelet count; Platelet transfusion; Rationale use
12.  Can we predict neonatal thrombocytopenia in offspring of women with idiopathic thrombocytopenic purpura? 
Blood research  2014;49(4):259-264.
Background
We aimed to investigate which factors in the clinical profile of mothers with idiopathic thrombocytopenic purpura (ITP) can predict neonatal risk of thrombocytopenia.
Methods
Data was retrospectively collected from all pregnant women with ITP who presented to our institution between 2001 and 2013. Neonatal offspring of these women were classified into 2 groups based on the presence or absence of neonatal thrombocytopenia (platelet count <100×109/L). Several parameters were compared between the 2 groups, including maternal age, maternal platelet count, maternal treatment history, and thrombocytopenia in siblings. We further examined the correlation between maternal platelet count at the time of delivery and neonatal platelet count at birth; we also examined the correlation between the minimum platelet counts of other children born to multiparous women.
Results
Sixty-six neonates from 49 mothers were enrolled in the study. Thrombocytopenia was observed in 13 (19.7%) neonates. Maternal treatment for ITP such as splenectomy did not correlate with a risk of neonatal thrombocytopenia. Sibling thrombocytopenia was more frequently observed in neonates with thrombocytopenia than in those without (7/13 vs. 4/53, P<0.01). No association was observed between maternal and neonatal platelet counts. However, the nadir neonatal platelet counts of first- and second-born siblings were highly correlated (r=0.87).
Conclusion
Thrombocytopenia in neonates of women with ITP cannot be predicted by maternal treatment history or platelet count. However, the presence of an older sibling with neonatal thrombocytopenia is a reliable risk factor for neonatal thrombocytopenia in subsequent pregnancies.
doi:10.5045/br.2014.49.4.259
PMCID: PMC4278008  PMID: 25548760
Idiopathic thrombocytopenic purpura; Pregnancy; Neonatal thrombocytopenia
13.  Thrombocytopenia in neonates and the risk of intraventricular hemorrhage: a retrospective cohort study 
BMC Pediatrics  2011;11:16.
Background
The overall prevalence of thrombocytopenia in neonates admitted to neonatal intensive care units ranges from 22 to 35%. There are only a few small studies that outline the relationship between the severity of thrombocytopenia and the risk of bleeding. This makes it difficult to form an evidence-based threshold for platelet transfusions in neonatal patients. The aim of this study was to determine the prevalence of thrombocytopenia in a tertiary neonatal intensive care unit and to study the relation between thrombocytopenia and the risk of intraventricular hemorrhage (IVH).
Methods
We performed a retrospective cohort study of all patients with thrombocytopenia admitted to our neonatal tertiary care nursery between January 2006 and December 2008. Patients were divided into 4 groups according to the severity of thrombocytopenia: mild (100-149 × 109/L), moderate (50-99 × 109/L), severe (30-49 × 109/L) or very severe (< 30 × 109/L). The primary outcome was IVH ≥ grade 2. Pearson's chi-squared and Fischer's exact tests were used for categorical data. ANOVA, logistic regression analysis and multivariate linear regression were used for comparisons between groups and for confounding factors.
Results
The prevalence of thrombocytopenia was 27% (422/1569). Risk of IVH ≥ grade 2 was 12% (48/411) in neonates with versus 5% (40/844) in neonates without thrombocytopenia (p < 0.01). After multivariate linear regression analysis, risk of IVH ≥ grade 2 in the subgroups of thrombocytopenic infants was not significantly different (p = 0.3).
After logistic regression analysis the difference in mortality rate in neonates with and without thrombocytopenia was not significant (p = 0.4). Similarly, we found no difference in mortality rate in the subgroups of neonates with thrombocytopenia (p = 0.7).
Conclusion
Although IVH ≥ grade 2 occurs more often in neonates with thrombocytopenia, this relation is independent of the severity of thrombocytopenia. Prospective studies should be conducted to assess the true risk of hemorrhage depending on underlying conditions. Randomized controlled trials are urgently needed to determine a safe lower threshold for platelet transfusions.
doi:10.1186/1471-2431-11-16
PMCID: PMC3045959  PMID: 21314921
14.  Platelet Activation Test in Unprocessed Blood (Pac-t-UB) to Monitor Platelet Concentrates and Whole Blood of Thrombocytopenic Patients 
Summary
Background
Platelet concentrate transfusion is the standard treatment for hemato-oncology patients to compensate for thrombocytopenia. We have developed a novel platelet activation test in anticoagulated unprocessed blood (pac-t-UB) to determine platelet function in platelet concentrates and in blood of thrombocytopenic patients.
Methods
We have measured platelet activity in a platelet concentrate and in anticoagulated unprocessed blood of a post-transfusion thrombocytopenic patient.
Results
Our data show time-dependent platelet activation by GPVI agonist (collagen related peptide; CRP), PAR-1 agonist (SFLLRN), P2Y12 agonist (ADP), and thromboxane receptor agonist (U46619) in a platelet concentrate. Furthermore, pac-t-UB showed time-dependent platelet activation in unprocessed blood of a post-transfusion patient with thrombocytopenia. Testing platelet function by different agonists in relation to storage show that 3-day-old platelet concentrates are still reactive to the studied agonists. This reactivity rapidly drops for each agonists during longer storage.
Discussion
Pac-t-UB is a novel tool to estimate platelet function by different agonists in platelet concentrates and in unprocessed blood of thrombocytopenic patients. In the near future, we will validate whether pac-t-UB is an adequate test to monitor the quality of platelet concentrates and whether pac-t-UB predicts the bleeding risk of transfused thrombocytopenic patients.
doi:10.1159/000350688
PMCID: PMC3638932  PMID: 23652405
Flow cytometry; Platelet, Platelet activation; Platelet concentrates; Platelet function; Platelet storage; Platelet transfusion; Platelets; Thrombocytopenia
15.  Role of platelet transfusion in the management of dengue patients in a tertiary care hospital 
Background and Objective:
While medical fraternity globally recognizes the role of platelet transfusion in the management of hospitalized dengue patients the exact indications and situations in which these are to be transfused may vary. Since there is inherent risk associated with the transfusion of blood/blood-component, it is imperative for each institution (or country) to lay their own criteria for transfusion of these blood components. The present study was conducted to lay precise criteria and transfusion trigger for platelet transfusion in our set-up.
Materials and Methods:
The present study was conducted on 225 serologically confirmed dengue patients admitted at Indraprastha Apollo Hospitals between 1st of August to 30th of November 2005. Clinical data, reports of hematological investigation, platelets requirements and data obtained from daily follow-up were analyzed. The clinicians followed the guidelines issued by the Directorate of Health services, NCT of Delhi.
Results:
In the serologically confirmed cases, the prevalence of thrombocytopenia (count less than 100,000/cumm) was 84.88% on admission and bleeding was recorded in 22 (9.7%) patients. About 96 (42.6%) patients of dengue cases received platelet transfusion. Among them 47 (20.88%) patients had a platelet count < 20,000/cumm, 43 (19.11%) had a platelet count in the range of 21-40,000/cumm while 6 (2.66%) patients had the platelet count in between 41 and 50,000/cumm. Out of 49 patients with a platelet count >20,000/cumm, 18 patients had haemorrhagic manifestations such as petechiae, gum-bleeding, epistaxis, etc., which necessitates the use of platelet transfusion. However, 31 patients received inappropriate platelet transfusion.
Conclusion:
This study suggests that bleeding occurs more often in patients with severe thrombocytopenia. High-risk patients having platelet count < 20,000/cumm and risk of bleeding require urgent platelet transfusion. Patients with platelet count 21-40,000/cumm are in moderate risk and require platelet transfusion only if they have any haemorrhagic manifestations and other superadded conditions.
doi:10.4103/0973-6247.28065
PMCID: PMC3168133  PMID: 21938225
Dengue patients; thrombocytopenia; platelet transfusion
16.  Perinatal Outcome of Pregnancies Complicated by Immune Thrombocytopenia 
Background
Immune thrombocytopenia (ITP) is an autoimmune disorder that leads to premature destruction of antibody-coated platelets. This study evaluated perinatal outcome and medications used for pregnancies complicated by ITP.
Methods
Medical records of 132 pregnancies belonged to 125 parturients with ITP who delivered between March 2001 and January 2011 were reviewed. Cases were included if diagnosed before pregnancy or if their platelet counts (PCs) were less than 80,000/µL during pregnancy without any other cause. Maternal and fetal outcomes were compared.
Results
Fifty six mothers (42.1%) had PC<50,000, 18 women (13.5%) developed preeclampsia and 15 (11.3%) were diabetics. Corticosteroid was used for120 cases (90.9%) and intravenous immunoglobulin for 14 women (10.5%). PCs of 114 neonates were available in the charts and 84 (83.2%) had PC>150,000/µL. Three neonates (2.3%) had PC<50 000, 31 neonates (23.3%) had preterm births and 32 (24.1%) needed NICU admissions. Fifty seven cases of ITP (43.2%) were diagnosed before pregnancy and 75 (56.8%) were diagnosed during pregnancy. There were 2 intrauterine fetal deaths and higher NICU admissions, 20 (34.48%) versus 12 (16%) in the first group (p=0.01).
Conclusion
Perinatal outcome of pregnancies with ITP is generally good. However neonates born from parturients with chronic ITP needed more NICU admissions.
PMCID: PMC3438436  PMID: 22997559
Immune thrombocytopenia; Perinatal; Outcome; Iran
17.  Evaluation of platelet cross-matching in the management of patients refractory to platelet transfusions 
Blood Transfusion  2014;12(2):187-194.
Background
Cross-match-compatible platelets are used to support thrombocytopenic patients who are refractory to randomly selected platelets. However, few studies have addressed the efficacy of using this strategy for patients requiring intensive platelet transfusion therapy. The aim of this study was to determine the effectiveness of cross-match-compatible platelets in an unselected group of patients refractory to platelets from random donors.
Materials and methods
A total of 406 cross-match-compatible platelet components were administered to 40 evaluable patients who were refractory to random-donor platelets. A solid-phase red cell adherence method was used for platelet cross-matching. The corrected count increment was used to monitor the effectiveness of each platelet transfusion. Multivariate analysis was performed to detect whether any variables could predict the response to transfusion.
Results
Statistically significant improvements were found in the mean corrected count increment when comparing cross-match-compatible platelets with randomly selected and incompatible platelets (p<0.001 for each). Compatible platelet transfusions were associated with a good response in 72.9% of cases while incompatible platelets were associated with a poor response in 66.7% of transfusion events (p<0.001). In the presence of clinical factors or alloimmunisation, compatible platelets were associated with good responses in 67.9% and 28.0% respectively vs 100% and 93.3% in their absence (p=0.009, p<0.001). Multivariate analysis revealed that cross-matching and alloimmunisation were the strongest predictors of transfusion response at 1 hour, while ABO compatibility, type of units received, followed by alloimmunisation then clinical factors were predictors at 24 hours.
Discussion
Platelet cross-matching using the solid-phase red cell adherence technique is an effective and rapid first-line approach for the management of patients refractory to platelet transfusions.
doi:10.2450/2014.0120-13
PMCID: PMC4039700  PMID: 24931840
platelets; cross-match; refractoriness; solid-phase red cell adherence method; corrected count increment
18.  Clinical Observation of Factors in the Efficacy of Blood Component Transfusion in Patients following Hematopoietic Stem Cell Transplantation 
PLoS ONE  2012;7(5):e36912.
Background
Factors affecting the efficacy of platelet and red blood cell (RBC) transfusion in patients undergoing hematopoietic stem cell transplantation (HSCT) have not been studied extensively. We aimed to evaluate platelet and RBC transfusion efficacy by measuring the platelet corrected count increment and the hemoglobin increment, respectively, 24 h after transfusion in 105 patients who received HSCT.
Methodology/Principal Findings
Using retrospective analysis, we studied whether factors, including gender, time of transplantation, the compatibility of ABO group between HSC donors and recipients, and autologous or allogenic transplantation, influence the efficacy of blood component transfusion. We found that the infection rate of HSCT patients positively correlated with the transfusion amount, and the length of stay in the laminar flow room was associated with transfusion. We found that platelet transfusion performed during HSCT showed significantly better efficacy than that performed before HSCT. The effect of platelet transfusion in auto-transplantation was significantly better than that in allo-transplantation. The efficacy of RBC transfusion during HSCT was significantly lower than that performed before HSCT. The efficacy of RBC transfusion in auto-transplantation was significantly higher than that in allo-transplantation. Allo-transplantation patients who received HSCs from compatible ABO groups showed significantly higher efficacy during both platelet and RBC transfusion.
Conclusions
We conclude that the efficacy of platelet and RBC transfusions does not correlate with the gender of patients, while it significantly correlates with the time of transplantation, type of transplantation, and ABO compatibility between HSC donors and recipients. During HSCT, the infection rate of patients positively correlates with the transfusion amount of RBCs and platelets. The total volume of RBC units transfused positively correlates with the length of the patients’ stay in the laminar flow room.
doi:10.1371/journal.pone.0036912
PMCID: PMC3365127  PMID: 22701516
19.  Hemostatic Function and Transfusion Efficacy of Apheresis Platelet Concentrates Treated with Gamma Irradiation in Use for Thrombocytopenic Patients 
Summary
Background
During the transfusion of blood components, the transfer of allogeneic donor white blood cells (WBCs) can mediate transfusion-associated graft-versus-host disease (TA-GVHD). To minimize the reaction, exposure of blood products to gamma irradiation is currently the standard of care. The aim of our study was to evaluate and compare hemostatic function, transfusion efficacy, and safety of gamma-irradiated single-donor apheresis platelet concentrates (PCs) and of conventional non-irradiated PCs in patients with chemotherapy-induced thrombocytopenia.
Methods
20 double-dose single-donor leukoreduced PCs were split in two identical units; one was gamma-irradiated with 25 Gy (study arm A) and the other remains non-irradiated (study arm B). Both units were stored under equal conditions. Hematologic patients were randomly assigned to receive gamma-irradiated or conventional non-irradiated PCs. Hemostatic function was evaluated by thrombelastography (TEG). TEG measurements were taken pre transfusion and 1 and 24 h post transfusion. TEG profiles were measured, noting the time to initiate clotting (R), the angle of clot formation (α), and the maximum amplitude (clot strength (MA)). Whole blood samples were collected from these thrombocytopenic patients at 1 and 24 h for PLT count increments (CIs) and corrected count increments (CCIs) with assessments of transfusion efficacy. Time to next PLT transfusion, transfusion requirement of RBCs, active bleeding, and adverse events (AEs), were analyzed.
Results
No differences could be found in hemostatic function parameters (MA, R, and α) between study arms A and B (all p values > 0.096) pre transfusion as well as 1 and 24 h post transfusion. No differences between study arms A and B were observed for mean (± standard deviation (SD)) 1-hour CCI (12.83 ± 6.33 vs. 11.59 ± 5.97) and 24-hour CCI (6.56 ± 4.10 vs. 5.76 ± 4.05). Mean 1-hour CI and 24-hour CI were not significantly different in both study arms (p = 0.254 and p = 0.242 respectively). Median time to the next PC transfusion after study PC was not significantly different between groups: (2.4 vs. 2.2 days, p = 0.767). No differences could be found in transfusion requirement of red blood cells (p = 0.744) between both study arms. There were also no regarding bleeding, adverse events, and acute transfusion reaction(s).
Conclusions
This study confirms safety of gamma-irradiated PCs for treatment thrombocytopenia. Hemostatic function, transfusion efficacy, bleeding, and safety of single-donor apheresis PCs treated with gamma irradiation versus untreated control PCs are comparable.
doi:10.1159/000363523
PMCID: PMC4086760  PMID: 25053932
Hemostatic function; Transfusion efficacy; Apheresis platelet concentrates; Gamma irradiation; Thrombocytopenic patients
20.  Differences in Platelet Function In Patients with Acute Myeloid Leukaemia and Myelodysplasia Compared to Equally Thrombocytopenic Patients with Immune Thrombocytopenia 
Background
Severe thrombocytopenia is a major risk factor for haemorrhage, and yet platelet function and bleeding risk at low platelet counts are poorly understood because of limitations of platelet function testing at very low platelet counts.
Objectives
To examine and compare platelet function in severely thrombocytopenic patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS) to patients with immune thrombocytopenia (ITP).
Methods
Whole blood flow cytometric measurement of platelet activation and platelet reactivity to agonists was correlated with the immature platelet fraction (IPF) and bleeding symptoms.
Results
Compared with patients with ITP, patients with AML/MDS had smaller platelets, lower IPF, and substantially lower platelet surface expression of activated GPIIb/IIIa and GPIb both with and without addition of ex vivo ADP or TRAP. In both ITP and AML/MDS, increased platelet surface GPIb on circulating platelets and expression of activated GPIIb/IIIa and GPIb on ex vivo activated platelets correlated with a higher IPF. Whereas platelet reactivity was higher for AML/MDS patients with bleeding than those with no bleeding, platelet reactivity was lower for ITP patients with bleeding than those with no bleeding.
Conclusions
AML/MDS patients have lower in vivo platelet activation and ex vivo platelet reactivity than patients with ITP. The proportion of newly-produced platelets correlates with the expression of platelet surface markers of activation. These differences might contribute to differences in bleeding tendency between AML/MDS and ITP. This study is the first to define differences in platelet function between AML/MDS patients and ITP patients with equivalent degrees of thrombocytopenia.
doi:10.1111/j.1538-7836.2011.04506.x
PMCID: PMC3210015  PMID: 21920014
Autoimmunity; bleeding; flow cytometry; haemorrhage; thrombocytopenia; thrombopoiesis
21.  Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1–risk myelodysplastic syndrome and thrombocytopenia 
Cancer  2014;120(12):1838-1846.
BACKGROUND
Thrombocytopenia in patients with myelodysplastic syndrome (MDS) is associated with shortened survival and an increased risk of evolution to acute myeloid leukemia (AML). In this study, the authors evaluated the efficacy of romiplostim in patients who had thrombocytopenia with low-risk/intermediate-1–risk MDS.
METHODS
Patients who had thrombocytopenia with low-risk/intermediate-1–risk MDS (N = 250) were randomized 2:1 to receive romiplostim or placebo weekly for 58 weeks.
RESULTS
The primary endpoint— the number of clinically significant bleeding events (CSBEs) per patient—had a hazard ratio for romiplostim:placebo of 0.83 (95% confidence interval, 0.66-1.05; P = .13). CSBEs were reduced significantly in the romiplostim group for patients who had baseline platelet counts ≥20 × 109/L (P < .0001). For patients who had baseline platelet counts <20 × 109/L, there was no difference in the number of CSBEs, but the platelet transfusion rates were higher in the placebo group (P < .0001), which may have affected the overall CSBE results in this group with severe thrombocytopenia. The incidence of bleeding events was reduced significantly in the romiplostim group (relative risk, 0.92), as were protocol-defined platelet transfusions (relative risk, 0.77). Platelet response rates according to 2006 International Working Group criteria were higher for the group that received romiplostim (odds ratio, 15.6). On the basis of interim data, an independent data monitoring committee advised halting study drug because of concerns regarding excess blasts and AML rates with romiplostim (interim hazard ratio, 2.51). At 58 weeks, the AML rates were 6% in the romiplostim group and 4.9% in the placebo group (hazard ratio, 1.20; 95% confidence interval, 0.38-3.84), and the overall survival rates were similar.
CONCLUSIONS
Romiplostim treatment in patients with low-risk/intermediate-1–risk MDS increased platelet counts and decreased the number of bleeding events and platelet transfusions. Although study drug was discontinued because of an initial concern of AML risk, survival and AML rates were similar with romiplostim and placebo.
doi:10.1002/cncr.28663
PMCID: PMC4298760  PMID: 24706489
romiplostim; myelodysplastic syndromes; drug therapy; thrombocytopenia; randomized controlled trial
22.  Dose of Prophylactic Platelet Transfusions and Prevention of Hemorrhage 
The New England journal of medicine  2010;362(7):600-613.
BACKGROUND
We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia.
METHODS
We randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1.1×1011, 2.2×1011, or 4.4×1011 platelets per square meter of body-surface area, respectively), when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary end point was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria).
RESULTS
In the 1272 patients who received at least one platelet transfusion, the primary end point was observed in 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were not significant). The incidences of higher grades of bleeding, and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9.25×1011) than in the medium-dose group (11.25×1011) or the high-dose group (19.63×1011) (P = 0.002 for low vs. medium, P<0.001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; P<0.001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (P<0.001).
CONCLUSIONS
Low doses of platelets administered as a prophylactic transfusion led to a decreased number of platelets transfused per patient but an increased number of transfusions given. At doses between 1.1×1011 and 4.4×1011 platelets per square meter, the number of platelets in the prophylactic transfusion had no effect on the incidence of bleeding. (ClinicalTrials.gov number, NCT00128713.)
doi:10.1056/NEJMoa0904084
PMCID: PMC2951321  PMID: 20164484
23.  Platelet transfusions: trigger, dose, benefits, and risks 
Over the last half century, platelet transfusion has been an effective therapy for the prevention and treatment of bleeding, particularly in patients with hematologic malignancies. Recent randomized trials have demonstrated that current practices may be suboptimal in a number of ways. The rationale for parsimony in the use of this powerful therapy includes previously described severe and fatal adverse outcomes (including refractoriness, hemolysis from ABO-mismatched transfusions, acute lung injury, and bacterial sepsis), newly described serious potential risks (including thrombosis and earlier leukemic recurrence), difficulty in maintaining adequate supplies of platelets, the need to place volunteer donors on cell separators to provide the product, and cost. Recent findings demonstrate that the platelet count threshold for prophylactic transfusion can be as low as 10,000/μL, and a therapeutic rather than a prophylactic strategy of transfusion for bleeding manifestations only may be equally safe for most patients. Another recently completed study suggests that very low doses of platelet transfusions (the equivalent of half a unit of apheresis platelets or two to three units of whole blood-derived platelets) are as effective at preventing bleeding as much higher doses. One question for which there are no randomized trial data is at what threshold prophylactic platelet transfusion should be given before invasive procedures or major surgery. The typically recommended threshold of 50,000/μL is based only on expert opinion, and substantial observational data indicate that this threshold leads to many transfusions that are likely unnecessary and therefore represent risk with little or no additional benefit.
doi:10.3410/M2-5
PMCID: PMC2874899  PMID: 20502614
24.  Platelet transfusions: trigger, dose, benefits, and risks 
Over the last half century, platelet transfusion has been an effective therapy for the prevention and treatment of bleeding, particularly in patients with hematologic malignancies. Recent randomized trials have demonstrated that current practices may be suboptimal in a number of ways. The rationale for parsimony in the use of this powerful therapy includes previously described severe and fatal adverse outcomes (including refractoriness, hemolysis from ABO-mismatched transfusions, acute lung injury, and bacterial sepsis), newly described serious potential risks (including thrombosis and earlier leukemic recurrence), difficulty in maintaining adequate supplies of platelets, the need to place volunteer donors on cell separators to provide the product, and cost. Recent findings demonstrate that the platelet count threshold for prophylactic transfusion can be as low as 10,000/µL, and a therapeutic rather than a prophylactic strategy of transfusion for bleeding manifestations only may be equally safe for most patients. Another recently completed study suggests that very low doses of platelet transfusions (the equivalent of half a unit of apheresis platelets or two to three units of whole blood-derived platelets) are as effective at preventing bleeding as much higher doses. One question for which there are no randomized trial data is at what threshold prophylactic platelet transfusion should be given before invasive procedures or major surgery. The typically recommended threshold of 50,000/µL is based only on expert opinion, and substantial observational data indicate that this threshold leads to many transfusions that are likely unnecessary and therefore represent risk with little or no additional benefit.
doi:10.3410/M2-5
PMCID: PMC2874899  PMID: 20502614
25.  Neonatal Hyperbilirubinemia in infants with G6PD c.563C > TVariant 
BMC Pediatrics  2012;12:126.
Background
There is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD) deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4–14% of hospitalized icteric neonates in Pakistan. G6PD c.563C > T is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having G6PD c.563C > T.
Methods
This was a case–control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. G6PDgenotype was analyzed in 32 deficient infants through PCR-RFLP analysis and gene sequencing.
Results
G6PD variants c.563C > T and c.131 C > G were observed in 21 (65%) and three (9%) of the 32 G6PD deficient infants, respectively. DNA of eight (25%) newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with c.563C > T variant had significantly lower enzyme activity (mean ± 1SD; 0.3 ± 0.2 U/gHb vs. 14.0 ± 4.5 U/gHb, p < 0.001) experienced higher peak levels of total serum bilirubin (mean ± 1SD; 16.8 ± 5.4 mg/dl vs. 13.8 ± 4.6 mg/dl, p = 0.008) which peaked earlier after birth (mean ± 1SD 2.9 ± 1.6 vs. 4.3 ± 2.3 days, p = 0.007). No statistically significant difference was observed in mean weight, age at presentation, hemoglobin, reticulocyte count, TSH level, hospital stay or in the frequency of initiation of phototherapy or blood exchange between the two groups.
Conclusions
We concluded that infants with G6PD c.563C > T variant developed jaundice earlier than infants with normal G6PD enzyme levels. Compared to G6PD normal infants, G6PD c.563C > T carrying infants had significantly low G6PD activity.
doi:10.1186/1471-2431-12-126
PMCID: PMC3529675  PMID: 22906047

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