Newborn Platelets Research Articles

Obstetric and neonatal outcomes of immune thrombocytopenic purpura in pregnancy and the role of delta hemoglobin index: A case-control study from a tertiary center.

To evaluate the effect of idiopathic thrombocytopenic purpura (ITP) on pregnancies and the role of the delta hemoglobin indices in the evaluation of treatment effectiveness. This case-control study was conducted with 23 ITP and 115 low-risk pregnancies. Obstetric outcomes (fetal growth retardation (FGR), preterm delivery) and neonatal outcomes (weights, APGAR scores, NICU admissions, thrombocytopenia) were recorded. ITP group was subgrouped based on the platelet ratio at the admission for delivery and evaluated the impact of platelet ratios on blood loss amounts at delivery by using delta hemoglobin indices. Eleven patients received treatment during pregnancy. The gestational age at birth and fetal APGAR scores were lower, and the preterm delivery and FGR rates were higher in the ITP group. Four newborns (17.4%) had thrombocytopenia. There were two postpartum hemorrhages. Newborn platelet counts did not correlate with maternal platelet counts. The study showed no difference in delta hemoglobin counts between the ITP and control groups. ITP is associated with an increased risk of maternal and fetal complications. The presented study showed by using the delta hemoglobin indices that, hemorrhagic complications could be prevented with appropriate management. Neonatal thrombocytopenia should be considered for all ITP patients.

Evaluation of serotonin levels in full-term newborns of diabetic mothers

BACKGROUND: The growth of neurological and mental diseases in the offspring of patients with pre- and gestational diabetes mellitus determines the need to study the regulatory function of the serotoninergic system of the brain in newborns. This plays a key role in its morphofunctional development in early ontogenesis, which is necessary for timely diagnosis of disorders and prevention of long-term consequences.
 AIM: The aim of this study was to evaluate serotonin levels in full-term newborns with diabetic fetopathy from mothers with pre- and gestational diabetes mellitus.
 MATERIALS AND METHODS: The main group consisted of 45 newborns with diabetic fetopathy, of whom 30 individuals were from mothers with type 1 diabetes mellitus and 15 ones from mothers with gestational diabetes mellitus. The control group comprised 20 healthy full-term newborns from healthy mothers without pregnancy complications. Serotonin concentrations were determined in platelet-rich plasma of blood from the umbilical cord vein, and in a platelet suspension prepared from venous blood taken on the first day of life, using high-performance liquid chromatography with electrochemical detection.
 RESULTS: Platelet-rich plasma serotonin level in umbilical cord blood taken from newborns of the main group was more than two times lower compared to children of healthy mothers. This parameter in venous blood taken from mothers with type 1 diabetes (0.744 ± 0.117 µmol/l) corresponded to that in healthy patients, while in mothers with gestational diabetes mellitus, it was significantly lower and amounted to 0.331 ± 0.071 µmol/l (p 0.05). Moreover, platelet-rich plasma serotonin level in all newborns correlated with that in their mothers (R = 0.505; p 0.05). Serotonin levels in venous blood platelets of newborns of the main group was almost 2.5 times lower than in healthy ones.
 CONCLUSIONS: The data obtained indicate the need to use platelet serotonin values as a biochemical marker of disorders of functional brain development in children with diabetic fetopathy.

ДИНАМИКА ФУНКЦИОНАЛЬНОЙ АКТИВНОСТИ ТРОМБОЦИТОВ У НЕДОНОШЕННЫХ НОВОРОЖДЕННЫХ ДЕТЕЙ С ИНФЕКЦИОННО-ВОСПАЛИТЕЛЬНЫМИ ЗАБОЛЕВАНИЯМИ В РАННЕМ НЕОНАТАЛЬНОМ ПЕРИОДЕ

Platelet involvement in inflammatory and immune responses and its functional activity in various pathological conditions are actively studied. Despite there are scientific publications characterizing platelets of newborns vs. adults the data on the features of the expression of activation markers on platelets of premature infants with a complicated course of the early neonatal period are not enough. The purpose of the research was to analyze the expression of glycoproteins and activation molecules on the surface of peripheral blood platelets in newborns with congenital infection depending on gestational age (GA). Materials and methods of research: a prospective single-center case-control study was conducted in the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after V.I. Kulakov (Moscow, Russia) in March 2018 - September 2019. The expression of activation markers on resting and activated platelets on the 1st and 3rd days of life (DOL) in 158 newborns aged 24 to 38 weeks was analyzed using the flow cytometry. The patients were divided into 3 groups: group 1 (n=20) of newborns with GA 24 to 28 weeks; group 2 (n=52) of newborns with GA of 29 to 33 weeks; and group 3 (n=86) of newborns with GA of 34 weeks and older. Results: in severely preterm (G1) compared with infants of older GA on the 3rd DOL platelets had higher MPV: 11.3 (10.4-12.3) vs. 10.1 (9.6-10.3), p=0.011, and PDW: 13.1 (12.2-15.6) vs. 11.3 (10.6-12.3), p<0.001. In infectious diseases in children with GA of 29 to 33 weeks there is a lower expression of phosphatidylserine on activated platelets in the 1st DOL: 8.8 (7.5-11.1) vs. 11.2 (10.3-12.1), p=0.046, and lower the content of activated platelets expressing P-selectin on the 3rd DOL: 89.5 (87.1-92.7) vs. 93.1 (90.4-94.4), p=0.048. In newborns with GA of 34 weeks and older with congenital infection in the 1st DOL there was a higher expression of von Willebrand Factor receptor revealed: 13.9 (12.3-16.4) vs. 12.4 (10.9-14.1), p=0.028, and a higher content of dense granules in activated platelets: 0.73 (0.65-0.79) vs. 0.67 (0.60-0.71), p=0.008. By the 3rd DOL there was an increase in MPV and PDW in all groups of children (p<0.05) recorded. Conclusion: in premature infants with congenital infection the expression of structural and activation molecules on platelets undergoes greater changes during the first three days of life than in children of similar GA without infectious pathology.

Serotonin and cyclic sleep organization in full-term newborn infants with intrauterine growth retardation

BACKGROUND: The high frequency of neurological and mental diseases in children who had intrauterine retardatiojn development indicates the need to study specific markers of disorders of fetal brain functional development, in particular, the state of the serotonergic system, which plays a key role in the morpho-functional development of the brain in early ontogenesis.
 AIM: To study the content of serotonin in full-term newborns with intrauterine development delay in comparison with quantitative and qualitative characteristics of sleep.
 MATERIALS AND MЕTHODS: The main group consisted of 26 newborns, whose intrauterine development took place in conditions of chronic placental insufficiency, which led to the formation of an asymmetric form of intrauterine retardatiojn development. The control group consisted of 72 healthy newborns from healthy mothers without pregnancy complications. Children of each group are divided into three subgroups depending on gestational age: I 37, II 38, III 3940 weeks. In all children, 712 hours after birth, an electropoligram of sleep was recorded (an electroencephalograph of the company Mizar, Russia) and its quantitative and qualitative analyses were carried out, highlighting the orthodox, paradoxical phase and undifferentiated state. The serotonin content was determined in platelet-rich plasma of blood from the umbilical cord vein after birth, as well as in a platelet suspension prepared from venous blood taken on the first day of life. The content of serotonin in platelets was judged by the indicator obtained by dividing the amount of serotonin in the platelet suspension by the platelet level. The amount of serotonin was determined by high-performance liquid chromatography with electrochemical detection. Statistical analysis was performed using the Statistica 6 program (Statsoft Inc, USA).
 RESULTS: We report here a low content of serotonin in platelet-rich plasma and platelets of newborns with intrauterine growth retardation and the absence of its normal increase in weeks 3739 of intrauterine development, as well as a violation of the genetic programming for the sleep-wake cycle organization.
 CONCLUSIONS: Assessment of the serotonin-producing system of the brain in comparison with the newborn sleep pattern can serve as a diagnostic marker of brain damage and substantiate the need for timely application of neuroprotection.

ABO Incompatibility between the Mother and Fetus Does Not Protect against Anti-Human Platelet Antigen-1a Immunization by Pregnancy.

(1) Background: ABO blood group incompatibility between the mother and fetus protects against anti-D immunization by pregnancy. The possible role of ABO incompatibility in protecting against anti-human platelet antigen-1a immunization is unclear. (2) Methods: This study retrospectively screened 817 families (mother-father-neonate trios) of suspected fetal and neonatal alloimmune thrombocytopenia for inclusion. ABO genotypes were determined in 118 mother-child pairs with confirmed alloimmune thrombocytopenia due to anti-HPA-1a antibodies, and 522 mother-child pairs served as the control group. The expression of blood group antigen A on platelets was determined in 199 consecutive newborns by flow cytometry and compared with adult controls. (3) Results: ABO incompatibility between mother and fetus did not protect against anti-human platelet antigen-1a immunization by pregnancy. ABO blood groups of mothers and/or fetuses were not associated with the severity of fetal and neonatal alloimmune thrombocytopenia. The expression pattern of blood group A antigens on the platelets of newborns mirrored that of adults, albeit on a lower level. Blood group A antigen was detected on a subpopulation of neonatal platelets, and some newborns revealed high platelet expression of A determinants on all platelets (type II high-expressers). (4) Conclusion: The lack of a protective effect of ABO incompatibility between mother and fetus against anti-human platelet antigen-1a immunization by pregnancy may indicate that fetal platelets are not the cellular source by which the mother is immunized.

Pancytopenia in a newborn due to maternal piperacillin and human leukocyte antigen antibodies

BackgroundPiperacillin antibody-induced immune hemolytic anemia is not rare in adults, and there have been reports of anti-HLA antibody-induced newborn platelet transfusion refractoriness. However, there has been no report of piperacillin-accompanied anti-HLA antibody-induced newborn pancytopenia. Case ReportWe herein present the case of a newborn with pancytopenia from a mother who carried anti-HLA-B55, anti-HLA-DR11, and piperacillin antibodies. The newborn HLA genotypes were HLA*B55:02 and HLA*DRB1*11:01. IgG antibodies can be transferred to the newborn via the placenta and induce the destruction of the platelet and white blood cells, which carry the corresponding antigens. Piperacillin antibodies coupling with newborn red blood cells (RBCs) led to the destruction of the RBCs and hemolytic anemia. ResultsThe direct anti-globulin test was positive for RBCs in the newborn, and piperacillin antibodies were positive in both the newborn and his mother. Anti-HLA antibodies were positive in the maternal serum, whereas homologous antigens were positive in the newborn. The direct anti-globulin test of platelet was weekly positive in the newborn. ConclusionPiperacillin and anti-HLA antibodies can pass through the placenta, induce incompatible blood cell destruction, and cause a series of clinical syndromes in newborns.

Morphofunctional features of platelets in premature newborns with very low and extremely low body weight

Background. Currently, the development of medicine in the field of perinatology is aimed at improving the quality of medical care for newborns, especially those born prematurely. Premature newborns are most likely to develop hemorrhagic disorders, which often aggravates their condition and determines high morbidity and mortality. On modern hematological analyzers, it has become possible to evaluate a larger number of blood parameters, including platelet parameters, however, there are a small number of studies devoted to the study of platelet parameters in premature newborns. The aim was to study the morphofunctional features of platelets in premature newborns with very low and extremely low body weight. Materials and methods. The study included 78 newborns born at 2534 weeks of gestation, with a body weight of less than 1500 grams. On the 3rd5th day of life, a clinical blood test was performed on the Advia 2120i hematological analyzer (Siemens), with the determination of platelet parameters: PLT, 103 cells/l, PCT, %, PDW, %, Large Plt, 103 cells/l, MPC, g/dl, MRM, pg. Results. In newborns with ELBW, a decrease in the number and granularity of platelets in the blood, an increase in the average dry mass of platelets was found. Newborns with intrauterine growth retardation have a reduced platelet count and reduced thrombocrit. In premature newborns with a gestational age of 2527 weeks, blood circulation of platelets with a reduced volume was established, and in newborns who were born at a gestational age of 3234 weeks with increased granularity. In the absence of antenatal prevention of respiratory distress syndrome in newborns, there is a decrease in thrombocrit, the number of platelets, including large forms in the blood. In premature newborns born in a state of severe asphyxia, a decrease in platelet granularity was noted. The use of high concentrations of O2 in the oxygen-air mixture during respiratory therapy leads to a decrease in the number of platelets in the blood. Conclusions. Factors determining the morphofunctional state of platelets in premature newborns were established: the presence of a full course of antenatal prevention of respiratory distress syndrome of newborns, gestational age, the severity of asphyxia at birth, as well as the concentration of O2 in the oxygen-air mixture used in respiratory therapy. Newborns with ELBW have a reduced platelet count, low-granulated platelets, and an increased average dry platelet mass. Newborns with intrauterine growth retardation have a reduced number of platelets and thrombocrit in the blood. The revealed morphofunctional features of platelets allow us to clarify the nature of changes in the platelet link of hemostasis in premature newborns for the timely prevention of complications during the underlying disease.

Neonatal Alloimmune Thrombocytopenia: A Concise Review.

Neonatal alloimmune thrombocytopenia (NAIT) is defined as an uncommon platelet disorder caused by maternal alloimmunization to human-specific antigens (HPAs) that are paternally inherited, resulting in low fetal/neonatal platelet levels and debilitating effects on the newborn. The incidence of NAIT is 1 in every 1000 live births within the United States; it is the most common cause of severe thrombocytopenia (<30 × 109/L) and intracranial hemorrhage in term newborns. The purpose of this article is to discuss the pathophysiology, clinical manifestations, diagnosis, and treatment of NAIT and its implications upon the lifespan of the neonate. A literature review was conducted using PubMed, CINAHL, and Google Scholar (2014-2019). Search terms included NAIT, neonatal/fetal alloimmune thrombocytopenia, newborn platelets, and intracranial bleeding and NAIT. NAIT can affect first pregnancies and often goes undiagnosed until delivery. Universal screening tools with a focus on HPA-1a typing via noninvasive testing have been successfully trialed and have yielded promising results indicating a 75% reduction in risks associated with NAIT; however, none have been incorporated into practice and prophylactic treatment remains unavailable. Adopting a universal screening tool and prophylaxis for NAIT would allow for early diagnosis and treatment in utero. Many healthcare providers are not familiar with NAIT often focusing on other causes of thrombocytopenia as a potential diagnosis.

Pregnancy of patients with idiopathic thrombocytopenic purpura: maternal and neonatal outcomes

Objective:Thrombocytopenia occurs in 7% of pregnant women. Along with other causes, idiopathic thrombocytopenic purpura (ITP), which is an autoimmune disease with autoantibodies causing platelet destruction, must be considered in the differential diagnosis. Antiplatelet antibodies can cross the placenta and cause thrombocytopenia in the newborn. The aim of our study was to assess the management of ITP in pregnancy, and to investigate neonatal outcomes.Material and Methods:This retrospective study was conducted in a tertiary center including 89 pregnant patients with ITP followed between October 2011 and January 2018. Patients were evaluated in two groups according to diagnoses of ITP and chronic ITP. Age, obstetric history, ITP diagnosis, and follow-up period, presence of splenectomy, platelet count during pregnancy and after birth, treatment during pregnancy, route of delivery, weight and platelet count of newborn, sign of hemorrhage, and fetal congenital anomaly were assessedResults:Considering the ITP and chronic ITP groups, no significant difference was seen with respect to parity, timing of delivery, preoperative and postoperative platelet counts, and hemoglobin values. Route of delivery, birth weight, APGAR scores, newborn platelet count, and congenital anomaly rates were also similar. The timing of treatment was different because patients whose diagnoses were established during pregnancy were mostly treated for preparation of delivery. Treatment modalities were similar.Conclusion:Probability of severe thrombocytopenia at delivery is higher in patients with ITP who are diagnosed during pregnancy when compared with patients who received prepregnancy diagnoses. ITP is an important disease for both the mother and newborn. Patients should be followed closely in cooperation with the hematology department.

Морфология тромбоцитов новорожденных детей по данным электронной микроскопии

Objective - to study the morphological features of platelets of newborns by using electron microscopy. Materials and methods. Peripheral blood platelets of healthy newborns were studied by means of transmission electron microscopy (TEM) method. The sample included 50 healthy babies from the Clinical Perinatal Center of Saratov region born at a gestational age of 37-42 weeks with an assessment on the Apgar scale (1952) at the first minute of at least 7 points. After blood sampling, platelet-rich plasma (PRP) was obtained by centrifugation. Results. As a result of the study, 3 forms of platelets were identified: 1. Inactive ones, rounded or more often oval-shaped, in which it is possible to see almost all intracellular structures being typical for platelets; 2. Activated forms that have long processes (pseudopods) and usually have no granules; 3. Transitional forms - apparently, platelets at the initial stages of activation: elements of their open tubular system are already expanding, and this leads to the appearance of vacuoles. However, they do not yet have a distinct rearrangement of the cytoskeleton, and, accordingly, long processes and a significant change in shape. Platelets of newborns are heterogeneous in morphofunctional state: most of them are represented by inactive forms 82(80-85)%, the smaller part includes activated 15(13-17)% and transitional forms 3(2-4)%. Platelet microparticles (PM) are platelet derivatives and are also variable in size and structure. They can be represented by simple vesicles without internal contents, or they can have secretory granules involved in the transmission of signaling information to other platelets and endothelial cells. In our study, several mechanisms of formation and separation of PM from “precursor platelets” were discovered, but their meaning is not yet fully understood and requires further study. Conclusion. This study demonstrates the heterogeneity of the platelet population of newborns associated with their morphofunctional state. For convenience of description, three morphological classes of platelets have been devised. The hypothesis about possible mechanisms of PM formation has been formulated.

5 Years' Experience of a Tertiary Center with Thrombocytopenic Pregnancies: Gestational Thrombocytopenia, Idiopathic Thrombocytopenic Purpura and Hypertensive Disorders of Pregnancy.

Aim To evaluate thrombocytopenic pregnancies including gestational thrombocytopenia (GT), idiopathic thrombocytopenic purpura (ITP), and hypertensive disorders of pregnancy (HDP). Materials and Methods We evaluated the pregnancy outcomes and laboratory findings of 385 patients diagnosed with GT, ITP, or HDP whose thrombocyte levels were < 150 000/µL. Results GT, ITP, and HDP were the final diagnoses in 315 (81.8%), 35 (9.1%), and 35 (9.1%) cases, respectively. Patients diagnosed during the 1st trimester and diagnosed with ITP had significantly lower minimal platelet counts during the antenatal period and prior to delivery (p < 0.001; p < 0.001; p < 0.001; p < 0.001). Transfusion of any kind of blood product was given in 9.9% (n = 38) of all cases. Twelve patients had methylprednisolone and/or intravenous immunoglobulin treatments during the antenatal period. All patients who had undergone medical treatment were also found to have ITP. Four out of 385 patients underwent hysterectomy post partum due to refractory hemorrhage. Analysis of newborn platelet levels showed no statistical differences between any of the groups. Despite the lack of statistical significance, the rate of thrombocytopenia in newborns was 50% in patients with severe thrombocytopenia, while rates were 25.6 and 18.1% in patients with moderate and mild thrombocytopenia, respectively. Conclusion Thrombocytopenic pregnancies must be carefully evaluated with regard to the severity of thrombocytopenia, gestational period at initial diagnosis, and etiology. In particular, patients with ITP must be evaluated carefully as these patients are more likely to require transfusions and have platelet counts < 50 × 10 3 /µl.

It's reticulated: the liver at the heart of atherosclerosis

Platelets play a critical role in both the initiation and progression of atherosclerosis, and even more so in the ensuing atherothrombotic complications. Low-dose aspirin remains the mainstay of antiplatelet therapy in high-risk patients by reducing the risk of myocardial ischemia, stroke or death due to cardiovascular disease. However, antiplatelet therapies lose their efficacy in people with diabetes mellitus, increasing the risk of future atherothrombotic events. The molecular mechanisms that promote platelet hyperactivity remain unclear but could be due to glycation-induced conformational changes of platelet membranes resulting in impaired aspirin entry or less-efficient acetylation/compensatory increase in COX-2 expression in newborn platelets. Emerging evidence from our laboratory and elsewhere suggest that enhanced platelet turnover (thrombopoiesis), particularly the production of immature reticulated platelets from the bone marrow, could contribute to atherosclerotic complications. We have identified a major role for neutrophil-derived S100A8/A9, a damage-associated molecular pattern, in driving reticulated thrombopoiesis by directly interacting with its receptors on Kupffer cells in the liver. In this review, we discuss the role of hepatic inflammation in driving reticulated platelet production and suggest potential targets to control their production, improve efficacy of current antiplatelet therapies and reduce the risk of atherothrombotic complications.

Recurrent severe gestational thrombocytopenia in pregnancy: a case report

Most of the newly diagnosed cases of thrombocytopenia in pregnancy are mild, asymptomatic and accidentally discovered on routine antenatal screening. Common causes for the same include gestational thrombocytopenia, Preeclampsia, HELLP syndrome, and less commonly immune causes like ITP. As a matter of fact, HELLP and Preeclampsia have specific diagnostic signs and symptomatology, others are rather difficult to distinguish, as they are usually asymptomatic. We present a case of 21 years second gravida at 35 weeks and six days period of gestation, referred from a local practitioner for severe thrombocytopenia (Platelet count-20000/mm3). She had history of previous still birth due to cord prolapse, and severe thrombocytopenia (Platelet count-6000/mm3) in previous pregnancy. She recovered rapidly and spontaneously in postpartum period. The newborn platelet count was also normal. She was considered to be a case of rare but severe recurrent gestational thrombocytopenia, after ruling out other causes of severe thrombocytopenia in pregnancy. Management includes adequate preparations for ensuring optimal fetomaternal outcome. Treatment initiation and modification should be done, with preparation and anticipation for regional anesthesia, blood loss and appropriate styptic measures.

A Non-Invasive Strategy for Neonatal Alloimmune Thrombocytopenia Diagnosis: Newborn Platelet Genotyping with Buccal Swabs

Neonatal alloimmune thrombocytopenia results from the maternal immune response against fetal-specific antigens inherited from the father. The diagnosis is ascertained only when the maternal alloantibody and the offending antigen present in the newborn are identified. Up until now most laboratories perform DNA extraction for neonatal genotyping from newborn blood samplings. In order to avoid such an invasive procedure, two protocols of DNA extraction from buccal swabs were developed: a manual protocol using the QIAamp mini blood kit (Qiagen), and an automated procedure with the MagNA Pure Compact instrument (Roche). Both EDTA-blood and buccal swabs from thrombocytopenic newborns were genotyped manually (14 samples), automatically (15 samples) or both manually and automatically (two samples). Human Platelet Antigen (HPA) genotyping was performed using the BeadChip assay (BioArray, Immucor). Concordant genotypings were obtained for all samples except for one swab with the manual method. The automated DNA extraction from newborn buccal swabs with the MagNA Pure Compact instrument was chosen as the first-line strategy, with a significant gain of time in processing buccal swabs.

Severe Gestational Thrombocytopenia: A Case Report and Brief Review of the Literature

Thrombocytopenia (TCP) is a common medical finding in obstetric population at term. The majority of new-onset TCP cases are mild, asymptomatic and diagnosed accidentally on routine antenatal screening. The most common causes at term are gestational thrombocytopenia (GT), preeclampsia/HELLP syndrome and immune-mediated thrombocytopenia (ITP). Preeclampsia/HELLP syndrome is accompanied with well-defined clinical characteristics and specific laboratory findings, while the other two are usually asymptomatic and are impossible to distinguish from one another. We encountered a case of new-onset TCP at 40 weeks gestation with negative history and a platelet count of 33 × 10 9 /L, yet, who had a fast spontaneous postpartum recovery. Her second pregnancy was also complicated by TCP of 77 × 10 9 /L at 37 weeks gestation. The newborn platelet count was normal in both instances. She was considered to have GT after a lapse of 4 years, being consistently healthy with normal platelet counts. After excluding other serious causes of severe new-onset TCP at term, management should be oriented towards securing hemostasis in preparation for delivery without wasting precious time and resources trying to discern between GT and ITP. J Hematol. 2016;5(4):142-150 doi: https://doi.org/10.14740/jh308w

Low-Dose versus Standard-Dose Intravenous Immunoglobulin to Prevent Fetal Intracranial Hemorrhage in Fetal and Neonatal Alloimmune Thrombocytopenia: A Randomized Trial

Objective: Pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) are commonly treated using weekly intravenous immunoglobulin (IVIG) at 1 g/kg maternal weight. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to evaluate the effectiveness of IVIG at a lower dose, i.e. 0.5 g/kg. Methods: This was a randomized controlled multicenter trial conducted in Sweden, the Netherlands and Australia. Pregnant women with human platelet antigen alloantibodies and an affected previous child without intracranial hemorrhage (ICH) were enrolled. The participants were randomized to IVIG at 0.5 or 1 g/kg per week. The analyses were per intention to treat. The primary outcome was fetal or neonatal ICH. Secondary outcomes were platelet count at birth, maternal and neonatal IgG levels, neonatal treatment and bleeding other than ICH. Results: A total of 23 women were randomized into two groups (low dose: n = 12; standard dose: n = 11). The trial was stopped early due to poor recruitment. No ICH occurred. The median newborn platelet count was 81 × 10⁹/l (range 8-269) in the 0.5 g/kg group versus 110 × 10⁹/l (range 11-279) in the 1 g/kg group (p = 0.644). Conclusion: The risk of adverse outcomes in FNAIT pregnancies treated with IVIG at 0.5 g/kg is very low, similar to that using 1 g/kg, although our uncompleted trial lacked the power to conclusively prove the noninferiority of using the low dose.

Antiplatelet therapy at the time of coronary artery surgery: can a personalized approach improve outcomes?

We read with great interest the recently published multicentre cohort study by Kremke et al. [1]. Patients exposed to antiplatelet therapy (APT) at the time of coronary artery surgery (CAS) had greater postoperative bleeding volumes and greater transfusion requirements [1]. Exposure to clopidogrel, but not aspirin, was associated with greater reoperation rates and was an independent risk factor for severe postoperative bleeding, although mean bleeding volumes were not significantly different in the aspirin and clopidogrel subgroups [1]. Despite current guidelines, it is apparent that many patients are proceeding with CAS without the 5-day delay off clopidogrel. The efficacy of platelet inhibition with clopidogrel varies widely among patients, from intensive platelet inhibition to poor platelet response [2], and these variations could, to some degree, explain the non-significant differences in mean bleeding volumes in the aspirin and clopidogrel subgroups [1]. The effect of clopidogrel on bleeding mainly depends on two factors: (i) observed platelet inhibition, which depends on inherent platelet activity prior to clopidogrel administration and platelet inhibitory response to clopidogrel and (ii) newborn platelets ability to restore normal aggregation after clopidogrel discontinuation. Therefore, the use of suitable point-of-care platelet function analysers seems to be reasonable in this field. Recently, we found aspirin(P = 0.014) and clopidogrel(P = 0.003) sensitive platelet function tests to be predictive of excessive postoperative bleeding in patients following CAS [2]. Of note, 76.3% patients were transfused with no significant differences among the groups with regard to the preoperative APT administration regime (P = 0.636) [2]. However, transfused patients had significantly lower values of aspirin-sensitive platelet function tests (P = 0.002) [2]. In our opinion, the study cohort is somehow heterogeneous. Eligible procedures were either isolated CAS or CAS combined with aortic valve replacement (AVR) [1]. AVR certainly extends the duration of cardiopulmonary bypass, which was recently described as a predictor of transfusion requirements [3]. After matching, authors reported a slightly greater use of antifibrinolytic drugs in the APT group [1]. Both on-pump and off-pump procedures were included [1]. Authors reported that off-pump surgery and perioperative use of tranexamic acid were associated with a lower risk of severe postoperative bleeding [1]. The use of antifibrinolytic drugs should be equally balanced since there is evidence that antifibrinolytic therapy reduces bleeding and transfusion outcomes [4]. It would be interesting to see if exclusion of CAS + AVR and off-pump CAS patients would bring different results. During the study period, thromboelastometry-guided blood component therapy became available at two of three participating centres [1]. At the same time, multivariate analysis revealed that surgery at one of the participating centres was one of independent risk factors for severe postoperative bleeding [1]. Spiess et al. [5] reported thromboelastography-guided haemostatic management to have significantly reduced the incidence of overall transfusion and mediastinal re-exploration due to excessive bleeding. Thus, perhaps one could assume that one centre, which was found to be independent risk factor for severe postoperative bleeding, was in fact the one without thromboelastometry guided transfusion therapy available. The largest extent of chest tube output together with the greatest transfusion rates, was observed in the subgroup of patients exposed to dual APT [1]. Those results are in line with the results recently published by Miceli et al. [6]. Further incremental platelet inhibition may be observed in the group of patients receiving dual APT. Therefore, the role of aspirin and clopidogrel administration management should be separately assessed by drug-specific platelet function tests, thus facilitating an individual therapeutic approach for discontinuation management of each antiplatelet agent preoperatively.

Letter by Petricevic and Biocina Regarding Article, “Platelet Function Measurement-Based Strategy to Reduce Bleeding and Waiting Time in Clopidogrel-Treated Patients Undergoing Coronary Artery Bypass Graft Surgery: The Timing Based on Platelet Function Strategy to Reduce Clopidogrel-Associated Bleeding Related to CABG (TARGET-CABG) Study”

HomeCirculation: Cardiovascular InterventionsVol. 5, No. 3Letter by Petricevic and Biocina Regarding Article, “Platelet Function Measurement-Based Strategy to Reduce Bleeding and Waiting Time in Clopidogrel-Treated Patients Undergoing Coronary Artery Bypass Graft Surgery: The Timing Based on Platelet Function Strategy to Reduce Clopidogrel-Associated Bleeding Related to CABG (TARGET-CABG) Study” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Petricevic and Biocina Regarding Article, “Platelet Function Measurement-Based Strategy to Reduce Bleeding and Waiting Time in Clopidogrel-Treated Patients Undergoing Coronary Artery Bypass Graft Surgery: The Timing Based on Platelet Function Strategy to Reduce Clopidogrel-Associated Bleeding Related to CABG (TARGET-CABG) Study” Mate Petricevic, MD and Bojan Biocina, MD, PhD Mate PetricevicMate Petricevic University of Zagreb School of Medicine University Hospital Center Zagreb Cardiac Surgery Department Zagreb, Croatia (Petricevic, Biocina) Search for more papers by this author and Bojan BiocinaBojan Biocina University of Zagreb School of Medicine University Hospital Center Zagreb Cardiac Surgery Department Zagreb, Croatia (Petricevic, Biocina) Search for more papers by this author Originally published1 Jun 2012https://doi.org/10.1161/CIRCINTERVENTIONS.112.970061Circulation: Cardiovascular Interventions. 2012;5:e47To the Editor:We read with great interest the recently published study by Mahla et al.1 The efficacy of platelet inhibition with aspirin and clopidogrel varies widely among patients from intensive platelet inhibition to poor platelet response.The effect of clopidogrel on bleeding mainly depends on 2 factors: (1) observed platelet inhibition, which is dependent on inherent platelet activity before clopidogrel administration and platelet inhibitory response to clopidogrel; and (2) newborn platelets' ability to restore normal aggregation after clopidogrel discontinuation. In addition to increased costs of hospitalization, clopidogrel discontinuation 5 days before coronary artery bypass surgery could place patients with high residual adenosine diphosphate-induced platelet-fibrin clot strength to risk of preoperative ischemic adverse events.The study enrolled patients with a wide range of aspirin daily dose, from 81 to 325 mg.1 Percent inhibition of arachidonic acid-induced aggregation did not differ between clopidogrel-naive and clopidogrel-treated patients despite treatment with lower aspirin doses observed in the clopidogrel-naive group.1 In addition, clopidogrel-treated patients had a more frequent history of coronary artery stenting.1 Was preoperative aspirin dose targeted after arachidonic acid-induced aggregation test to achieve adequate platelet inhibitory response? If so, can we assume that a higher proportion of clopidogrel-treated patients had a poor platelet-inhibitory response to lower aspirin doses?There is evidence that certain patients have an accentuated response to the usual doses of preoperative aspirin that may result in increased perioperative blood loss.2 It would be very valuable if authors correlated arachidonic acid-induced aggregation test values with chest tube drainage. Did authors detect patients with accentuated response to aspirin and compare chest tube drainage between patients with respect to presence of pronounced versus poor platelet inhibitory response to aspirin treatment? In our opinion, when assessing the influence of preoperative antiplatelet therapy administration management on bleeding and adverse ischemic events, the role of aspirin should inextricably be included in considerations by objective quantification.Adenosine diphosphate-induced platelet-fibrin clot strength cutoff associated with ischemia in patients with coronary artery disease undergoing stenting is not a reliable surrogate for adequate hemostasis. A correlation between drug-specific platelet function test (adenosine diphosphate-induced platelet-fibrin clot strength and arachidonic acid-induced aggregation test) with chest tube drainage could bring the most precise and reliable cutoff values that delineating bleeding tendency.The role of aspirin and clopidogrel on bleeding should separately be assessed by drug-specific platelet function tests, facilitating an individual therapeutic approach for each antiplatelet agent preoperatively. Such an approach could distinguish patients with high residual platelet activity, thus proclivity to ischemic events, or enhanced platelet inhibition, thus proclivity to excessive bleeding. In a group of patients with pronounced platelet inhibition after aspirin administration, early aspirin discontinuation should be considered. Such an approach requires further studies to provide cutoff values that predict excessive chest tube drainage and, according to obtained cutoff values, evaluate antiplatelet therapy management in the context of chest tube drainage and clinical outcome.We congratulate the authors on their elegant and timely research.Mate Petricevic, MDBojan Biocina, MD, PhD University of Zagreb School of Medicine University Hospital Center Zagreb Cardiac Surgery Department Zagreb, CroatiaDisclosuresNone.

How to prevent bleeding events in on- and off-pump coronary artery bypass patients exposed to clopidogrel preoperatively

The effect of clopidogrel on bleeding mainly depends on two factors: (1) observed platelet inhibition, which is depending on inherent platelet activity prior to clopidogrel administration and platelet inhibitory response to clopidogrel and (2) newborn platelets ability to restore normal aggregation after clopidogrel discontinuation.The role of aspirin and clopidogrel on bleeding should separately be assessed by drug specific platelet function tests, facilitating individual therapeutic approach for each antiplatelet agent preoperatively. Such an approach could distinguish patients with high residual platelet activity, thus proclivity to ischemic events, or enhanced platelet inhibition, thus proclivity to excessive bleeding. It would be interesting if authors compared preoperative ischemic events incidence between patients groups with respect to preoperative clopidogrel treatment. Timing of discontinuation as well as intensity of preoperatively administered aspirin and clopidogrel should be tailored according to drug specific platelet function tests in order to minimize both ischemic and bleeding events. In group of patients with pronounced platelet inhibition after aspirin and/or clopidogrel administration, early antiplatelet drug discontinuation should be considered. For elective patients, delaying of surgery in cases of pronounced platelet inhibition after antiplatelet drugs administration should be considered if clinically condition allows. For urgent and/or emergent cases with observed preoperative deep platelet inhibition, the desmopressin administration should be considered [5] as well as intraoperative thromboelastography guided hemostatic therapy which significantly reduces incidence of overall transfusion and mediastinal re-exploration due to excessive bleeding [6]. However, such an approach requires further studies in order to provide platelet function test cut-off values that delineate bleeding as well as ischemic events. According to obtained cut-off values, antiplatelet therapy management should be evaluated in context of clinical outcome.

Prediction of the fetal status in noninvasive management of alloimmune thrombocytopenia

AbstractFetal/neonatal alloimmune thrombocytopenia is the most common cause of severe thrombocytopenia in the fetus and in an otherwise healthy newborn. To counter the consequences of severe fetal thrombocytopenia, antenatal therapies have been implemented. Predictive parameters for fetal severe thrombocytopenia are important for the development of noninvasive strategy and tailored intervention. We report here data concerning 239 pregnancies in 75 HPA-1bb women. Analysis of the index cases (diagnosis of fetal/neonatal alloimmune thrombocytopenia) did not show any significant correlation between the severity of the disease and the maternal genetic background (ABO blood group and HLA-DRB3 allele). Subsequent pregnancies were managed, and therapy effectiveness was evaluated. The highest mean newborn platelet count was observed for a combination of intravenous immunoglobulin and steroids (135 × 109/L; 54 newborns) compared with intravenous immunoglobulin alone (89 × 109/L; 27 newborns). The maternal anti-HPA-1a antibody concentration measured before any treatment and before 28 weeks of gestation was predictive of the fetal status. The weighted areas under curves of the maternal alloantibody concentrations were predictive of therapy response. To conclude, this large retrospective survey gives new insights on maternal predictive parameters for fetal status and therapy effectiveness allowing noninvasive strategies.