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Blood group or red cell alloimmunization occurs when a pregnant patient has produced antibodies to a blood group antigen possessed by the fetus and not possessed by the pregnant patient. Maternal antibodies are usually produced as an immune response to fetal-maternal bleeding or blood product transfusion. Prevention remains the most important strategy to avoid the formation of maternal antibodies or alloimmunization. Maternal alloimmunization may result in transplacental passage of these antibodies into the fetal circulation and the potential for fetal or neonatal hemolysis and anemia. Red cell alloimmunization can result in significant perinatal morbidity and mortality. Management of alloimmunization in pregnant patients should be protocol-driven. Current strategies for assessment and therapies allow for more thorough and less invasive management with risks to mother and fetus., (Copyright © 2024 by the American Academy of Pediatrics.)

Background and Objectives: Pregnancy in women with sickle cell disease (SCD) is associated with severe complications. Red blood cell (RBC) alloimmunisation is a worrying situation in pregnant women with SCD. This could increase the difficulty in finding a pheno-compatible red blood product. Our study aimed to determine the prevalence of RBC alloantibodies in pregnant women with SCD and to determine the risk factors for alloantibodies formation., Methods/materials: We conducted a prospective study at the "Centre National de Transfusion Sanguine de Bamako" from August 2022 to January 2023. For each participant, we collected important information, including obstetrical and transfusion histories. We performed ABO group, Rh and Kell phenotyping, and antibody screening in all study participants. We performed statistical analysis., Results: We recruited 95 pregnant women with SCD. In our study, 62% of our participant had a history of blood transfusion. Only 23% of our pregnant women with SCD had a history of miscarriage. The prevalence of RBC alloantibodies was 14%. The main antibodies detected were anti-E (38%) and pan-agglutinins (23%). Miscarriage history, blood transfusion history, and pregnancy number were the main risk factors for RBC alloimmunisation., Conclusion: The care of pregnant women with SCD is complex and requires collaboration between haematologists, clinicians and gynaecologists. National guidelines should be implemented to make ABO and D typing, Rh and Kell phenotyping and antibody screening routine for all pregnant women. This would facilitate early detection of high-risk situations. Particular attention should be paid to SCD pregnant women with miscarriage and blood transfusion histories., (© 2024 British Blood Transfusion Society.)

Background: Antiphospholipid antibody syndrome (APS) is a systemic, autoimmune, prothrombotic disease characterized by persistent antiphospholipid antibodies, thrombosis, recurrent abortion, complications during pregnancy, and occasionally thrombocytopenia. At present, there is no consensus on the treatment of this disease. Long-term anticoagulation is recommended in most cases in patients with thrombotic APS. This study aimed to evaluate whether aspirin combined with low-molecular-weight heparin (LMWH) can improve the live birth rate in antiphospholipid syndrome and its correlation with D-dimer., Methods: The data were retrieved from the WanFang Data, CBM, VIP, CNKI, the Cochrane Library, PubMed, EMBASE, OVID, and Web of Science databases. We collected data on randomized controlled trials of aspirin combined with LMWH in the treatment of pregnant women with APS. The "Risk of Bias Assessment" tool and the "Jadad Scale" provided by the Cochrane Collaboration were used to evaluate the risk of bias and quality of the collected literature. The risk ratio (RR) and its 95% confidence interval (CI) were determined using Statase-64 software., Results: In this study, a total of 11 studies were included, comprising a total of 2101 patients. The live birth rate in pregnant women with APS was higher on administration of aspirin combined with LMWH than with aspirin alone (RR = 1.29, 95% CI = 1.22-1.35, P < .001). d-dimer concentration in plasma predicted the live birth rate, which was higher below the baseline than above it (RR = 1.16, 95% CI = 1.09-1.23, P < .001). The subgroup analysis of the live birth rate was carried out based on the course of treatment, and the results were consistent with the overall results. Begg funnel plot test revealed no publication bias. Sensitivity analysis showed that deleting any study did not affect the results., Conclusion: Aspirin combined with LMWH for APS may improve live birth rate, and detection of d-dimer levels in APS pregnant women may predict pregnancy complications and guide the use of anticoagulants., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Antiphospholipid syndrome (APS) is an acquired thrombophilia characterized by recurrent thrombosis and/or pregnancy morbidity, in the presence of antibodies to β2 glycoprotein-I (β2GPI), prothrombin or Lupus anticoagulant (LA). Anti-β2GPI antibodies recognize complexes of β2GPI dimers with CXCL4 chemokine and activate platelets. Thrombospondin 1 (TSP-1) is secreted by platelets and exhibits prothrombotic and proinflammatory properties. Therefore, we investigated its implication in APS., Methods: Plasma from APS patients (n = 100), Systemic Lupus Erythematosus (SLE) (n = 27) and healthy donors (HD) (n = 50) was analyzed for TSP-1, IL-1β, IL-17A and free active TGF-β1 by ELISA. Human Umbilical Vein Endothelial Cells (HUVECs) and HD monocytes were treated with total HD-IgG or anti-β2GPI, β2GPI and CXCL4 and CD4 + T-cells were stimulated by monocyte supernatants. TSP-1, IL-1β, IL-17A TGF-β1 levels were quantified by ELISA and Real-Time PCR., Results: Higher plasma levels of TSP-1 and TGF-β1, which positively correlated each other, were observed in APS but not HDs or SLE patients. Patients with arterial thrombotic events or those undergoing a clinical event had the highest TSP-1 levels. These patients also had detectable IL-1β, IL-17A in their plasma. HD-derived monocytes and HUVECs stimulated with anti-β2GPI-IgG-β2GPI-CXCL4 secreted the highest TSP-1 and IL-1β levels. Supernatants from anti-β2GPI-β2GPI-CXCL4 treated monocytes induced IL-17A expression from CD4 + T-cells. Transcript levels followed a similar pattern., Conclusions: TSP-1 is probably implicated in the pathogenesis of APS. In vitro cell treatments along with high TSP-1 levels in plasma of APS patients suggest that high TSP-1 levels could mark a prothrombotic state and an underlying inflammatory process., (Copyright © 2020. Published by Elsevier Ltd.)

Background:  Anticardiolipin (aCL) and anti-β2 glycoprotein I (aβ2GPI) immunoglobulin A (IgA) antiphospholipid antibodies (aPL) have shown to associate with thrombosis and pregnancy morbidity. However, inclusion of IgA aPL in the classification criteria of the antiphospholipid syndrome (APS) has been debated. We investigated the value of aCL and aβ2GPI IgA aPL in the detection of thrombosis and pregnancy morbidity in addition to the current aPL panel for APS., Methods:  We included 1,068 patients from eight European medical centers: 259 thrombotic APS patients, 122 obstetric APS patients, 204 non-APS thrombosis patients, 33 non-APS obstetric patients, 60 APS patients with unspecified clinical manifestations, 196 patients with autoimmune diseases, and 194 controls. aCL and aβ2GPI IgG/M/A were detected with four commercial assays and lupus anticoagulant was determined by the local center., Results:  Positivity for IgA aPL was found in 17 to 26% of the patients with clinical manifestations of APS and in 6 to 13% of the control population. Both aCL and aβ2GPI IgA were significantly associated with thrombosis and pregnancy morbidity. Isolated IgA positivity was rare in patients with clinical manifestations of APS (0.3-5%) and not associated with thrombosis and/or pregnancy morbidity. Addition of IgA to the current criterion panel did not increase odds ratios for thrombosis nor pregnancy morbidity., Conclusion:  aCL and aβ2GPI IgA are associated with clinical manifestations of APS. However, isolated IgA positivity was rare and not associated with thrombosis or pregnancy morbidity. These data do not support testing for aCL and aβ2GPI IgA subsequent to conventional aPL assays in identifying patients with thrombosis or pregnancy morbidity., Competing Interests: G. W. Moore reports consultancy fees from Technoclone, outside the submitted work. W. Chayoua, D. Yin, and B. de Laat are employees of Synapse Research Institute, part of Diagnostica Stago SAS. The other authors state that they have no relevant conflict of interest., (Thieme. All rights reserved.)

Importance: Immune thrombocytopenia purpura (ITP), an autoimmune disease characterized by destruction of platelets, is a hematological disorder that can present in both pregnant and nonpregnant patients. Although thrombocytopenia in pregnancy can be caused by more common pathologies such as gestational thrombocytopenia and preeclampsia, ITP can present initially during pregnancy, further complicating diagnosis. Management must be considerate of both the pregnancy itself and the fetus., Objective: Review the diagnosis, treatment, and management of ITP in pregnancy based on current recommendations., Evidence Acquisition: Review articles, original research, and case studies were utilized., Results: Throughout pregnancy, patients are screened for a variety of conditions or disorders of pregnancy. Thrombocytopenia is a common pathology of pregnancy, but ITP is a rare condition that a provider needs to be aware of. After ruling out secondary causes of thrombocytopenia or more common causes such as gestational thrombocytopenia or preeclampsia, ITP should be considered. After diagnosis, treatment options should be discussed and initiated to provide safety for both the mother and fetus., Conclusions: After reading this article, the reader will understand the current recommendations regarding the diagnosis, treatment, and management of ITP in pregnancy., Relevance: The practitioner will be comfortable treating this condition during pregnancy.

Purpose: Neonatal immune neutropenia is observed in rare cases in newborns from mothers with idiopathic or autoimmune neutropenia, secondary to passive transfer of maternal granulocyte auto-antibodies., Methods: We performed a literature review and report four supplementary cases from the French registry of neutropenia., Results: Only 14 cases (11 mothers, 14 newborns) have been reported. Granulocyte aggregation (GAT) and granulocyte indirect immunofluorescence test (GIFT) are the recommended laboratory procedures for antibody detection. Monoclonal antibody-specific immobilization of granulocyte antigens (MAIGA)-confirmed antibody specificity. Antibody detection in newborns is not generally possible owing to extreme neutropenia. In half of the cases autoantibodies against neutrophils (AAN) were positive in maternal sera (7 out of 11). In some newborns tested, IgG + AAN were also positive, with disappearance in parallel of spontaneous neutrophil count improvement. No correlation between maternal type of AAN and titer and neonatal neutropenia can be established. Neutropenia resolved spontaneously between 2 weeks and 4 months. Infections in newborns were observed in 43% of cases, with no deaths reported. Granulocyte colony-stimulating factor (G-CSF) was administered to some newborns (5 out of 14) in the case of infections. Low-dose G-CSF administered to childbearing women during pregnancy could be proposed to prevent neutropenia in newborns., Conclusions: From the few cases reported so far it is impossible to draw any conclusions regarding frequency, risk factors, and outcome, but the overall prognosis for newborns seems good. Because it can be associated with potentially severe neonatal infections, autoimmune neutropenia in childbearing mothers should be closely monitored in collaboration with gynecologists and pediatricians.

Objective: To evaluate the cost-effectiveness of high-throughput, non-invasive prenatal testing (HT-NIPT) for fetal Rhesus D (RhD) genotype to guide antenatal prophylaxis with anti-D immunoglobulin compared with routine antenatal anti-D immunoglobulin prophylaxis (RAADP)., Design: Cost-effectiveness decision-analytic modelling., Setting: Primary care., Participants: A simulated population of 100 000 RhD-negative women not known to be sensitised to the RhD antigen., Methods: A decision tree model was used to characterise the antenatal care pathway in England and the long-term consequences of sensitisation events. The diagnostic accuracy of HT-NIPT was derived from a systematic review and bivariate meta-analysis; estimates of other inputs were derived from relevant literature sources and databases. Women in whom the HT-NIPT was positive or inconclusive continued to receive RAADP, whereas women with a negative result received none. Five alternative strategies in which the use of HT-NIPT may affect the existing postpartum care pathway were considered., Main Outcome Measures: Costs expressed in 2015GBP and impact on health outcomes expressed in terms of quality-adjusted life-years over a lifetime., Results: The results suggested that HT-NIPT appears cost saving but also less effective than current practice, irrespective of the postpartum strategy evaluated. A postpartum strategy in which inconclusive test results are distinguished from positive results performed best. HT-NIPT is only cost-effective when the overall test cost is £26.60 or less., Conclusions: HT-NIPT would reduce unnecessary treatment with routine anti-D immunoglobulin and is cost saving when compared with current practice. The extent of any savings and cost-effectiveness is sensitive to the overall test cost., Tweetable Abstract: HT-NIPT is cost saving compared with providing anti-D to all RhD-negative pregnant women., (© 2018 Royal College of Obstetricians and Gynaecologists.)

The role of prophylactic transfusion therapy for the treatment of sickle cell disease during pregnancy is unclear. An analysis of the existing literature shows a limited number of publications that address this issue and specifically compare clinical outcomes in this population based on a treatment strategy of prophylactic transfusion versus transfusion only for clinical indications (on-demand transfusion). The existing studies show a wide variation in study design and outcomes measured. The results of this analysis suggest that there are insufficient data to support a clinically significant difference in morbidity and mortality outcomes based on transfusion strategy. Additional prospective clinical studies need to be performed to adequately address the risks and benefits of prophylactic transfusion and guide clinical decision making., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Red blood cell (RBC) alloimmunization during pregnancy is still a major problem. Historically, anti-D antibodies are most likely to cause severe hemolysis, but other antibodies are also important. In Iceland, postnatal RhIg prophylaxis was implemented in 1969, universal RBC antibody screening was implemented in 1978, but antenatal RhIg prophylaxis is not yet routine., Study Design and Methods: This nation-wide population study gathered data on alloimmunized pregnancies in Iceland between 1996 and 2015. Blood bank alloimmunization data were linked to Icelandic Medical Birth Registry data. RBC antibodies were classified as either clinically significant or clinically nonsignificant., Results: In total, 912 positive antibody screens from 87,437 births were identified (1.04% prevalence). The most frequent antibodies were anti-M (19.4%), anti-E (19.0%), and anti-D (12.5%). Anti-D prevalence among D-negative mothers was 1.1%. Icelandic Medical Birth Registry data were available for 881 (96.6%) pregnancies. In the clinically significant group (n = 474), anti-E (27%) and anti-D (20%) were most common, whereas anti-M was most frequent (53%) in the clinically nonsignificant group (n = 407). Mothers in the clinically significant group were older, more often multigravidae, had more abortions and stillbirths, and had shorter gestational length. Newborns in the clinically significant group were less healthy, had lower weight and Apgar scores, and required more treatment. Among specificities in the clinically significant group, anti-D antibodies were most strongly associated with severe hemolysis., Conclusion: In this study, the prevalence of alloimmunization was similar to that in previous reports. Of all clinically significant antibodies, anti-D was most strongly associated with severe hemolysis, requiring phototherapy or exchange transfusions. Our data emphasize the importance of implementing an antenatal prophylactic RhIg program in Iceland in the near future., (© 2017 AABB.)

Acquired hemophilia A (AHA) is a severe bleeding disorder caused by autoantibodies against clotting factor VIII (FVIII). With an estimated annual incidence of 1.3 to 1.5 per million, AHA is a rare disease. An extremely rare form of AHA has been described among women in the peripartum period, and may present with peripartum hemorrhage. Notably, although hemorrhagic symptoms commonly present 1-4 months around delivery, they may occur up to 1 year after parturition. When caring for a mother with AHA it is important to note that Factor VIII inhibitor may be transferred via the placenta from the mother to the fetus. Hence the newborn may also be affected. It is important to increase the awareness of Gynecologists for clinical symptoms and laboratory signs of AHA in order to avoid delayed diagnosis. Treatment may involve use of bypass agents to control hemorrhage, despite the risk of thrombosis, while immunomodulation (with increasing role for Rituximab) may be required to eradicate the inhibiting antibodies. Our review will evaluate the epidemiology, diagnosis, clinical course and treatment of peripartum AHA, focusing upon mother and infant care., (© 2017 Elsevier Ltd. All rights reserved.)

Objective: The objective of this study was to describe complement activation in hemostatic and pathologic states of coagulation and in the acquired and congenital hemolytic anemias., Methods and Results: We review published and emerging data on the involvement of the classic, alternative and lectin-based complement pathways in coagulation and the hemolytic anemias. The alternative pathway in particular is always "on," at low levels, and is particularly sensitive to hyper-activation in a variety of physiologic and pathologic states including infection, autoimmune disorders, thrombosis and pregnancy, requiring tight control predicated on a variety of soluble and membrane bound regulatory proteins. In acquired hemolytic anemias such as paroxysmal nocturnal hemoglobinuria (PNH) and cold agglutinin disease (CAD), the complement system directly induces red blood cell injury, resulting in intravascular and extravascular hemolysis. In congenital hemolytic anemias such as sickle cell disease and β-thalassemia, the complement system may also contribute to thrombosis and vascular disease. Complement activation may also lead to a storage lesion in red blood cells prior to transfusion., Conclusion: Complement pathways are activated in hemolytic anemias and are closely linked with thrombosis. In acquired disorders such as PNH and possibly CAD, inhibition of the alternative complement pathway improves clinical outcomes and reduces thrombosis risk. Whether complement inhibition has a similar role in congenital hemolytic anemias apart from the atypical hemolytic-uremic (aHUS)-type thrombotic microangiopathies remains to be determined., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

C4b-binding protein (C4BP) is best known as a potent soluble inhibitor of the classical and lectin pathways of the complement system. This large 500 kDa multimeric plasma glycoprotein is expressed mainly in the liver but also in lung and pancreas. It consists of several identical 75 kDa α-chains and often also one 40 kDa β-chain, both of which are mainly composed of complement control protein (CCP) domains. Structure-function studies revealed that one crucial binding site responsible for inhibition of complement is located to CCP1-3 of the α-chain. Binding of anticoagulant protein S to the CCP1 of the β-chain provides C4BP with the ability to strongly bind apoptotic and necrotic cells in order to prevent inflammation arising from activation of complement by these cells. Further, C4BP interacts strongly with various types of amyloid and enhances fibrillation of islet amyloid polypeptide secreted from pancreatic beta cells, which may attenuate pro-inflammatory and cytotoxic effects of this amyloid. Full deficiency of C4BP has not been identified but non-synonymous alterations in its sequence have been found in haemolytic uremic syndrome and recurrent pregnancy loss. Furthermore, C4BP is bound by several bacterial pathogens, notably Streptococcus pyogenes, which due to inhibition of complement and enhancement of bacterial adhesion to endothelial cells provides these bacteria with a survival advantage in the host. Thus, depending on the context, C4BP has a protective or detrimental role in the organism., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Immune thrombocytopenia (ITP) in pregnant women can cause neonatal thrombocytopenia by transport of antiplatelet autoantibodies across the placenta. Usually, an infant's platelet count normalizes within 2 months. We observed neonatal thrombocytopenia that persisted more than 4 months and disappeared following discontinuation of breastfeeding. The aim of our study was to discern whether breast milk of ITP mothers contained antiplatelet antibodies causing persistent thrombocytopenia. We collected milk samples from 3 groups of women: ITP group, 7 women who had ITP during pregnancy; R-ITP group, 6 women who recovered from ITP before pregnancy; and 9 healthy controls. We found increased levels of antiplatelet antibodies of the immunoglobulin A type in the milk of ITP patients compared with the other 2 groups. Similar increase was demonstrated for antibodies binding to αIIbβ3 expressed in cultured cells. Thus, transfer of antiplatelet antibodies from ITP mothers by breastfeeding can be associated with persistent neonatal thrombocytopenia., (© 2015 by The American Society of Hematology.)

Background: The rare amorph Rhnull phenotype is caused by silent alleles at the RH locus and usually arises in consanguineous families. To date, only five molecular backgrounds have been identified in five unrelated families. Subjects with Rhnull red blood cells (RBCs) readily produce alloantibodies to high-prevalence Rh antigens., Study Design and Methods: RBCs from a pregnant woman (G5P3) from Libya, with a positive indirect antiglobulin test were phenotyped by hemagglutination. RHD and RHCE genes were analyzed at the genomic level and mutation inheritance pattern was assessed in the patient's family., Results: Hemagglutination testing showed a D-C-E-c-e- phenotype in the proposita associated with the presence of a high titer anti-Rh29 (4096). Molecular analysis revealed a deletion of RHD and presence of a novel RHCE allele with a 7-bp duplication in Exon 7. This duplication is predicted to introduce a frameshift after His350, a new C-terminal sequence, and a premature stop codon resulting in shortened predicted protein with only 402 amino acids. The mutated allele was found at homozygous state in the proposita and heterozygous state in her parents and one brother., Conclusion: This report describes a novel RHCE mutation causing the loss of RhCE antigen expression in association with RHD deletion, leading to an amorph Rhnull phenotype., (© 2014 AABB.)

Problem: Thrombophilia is associated with pregnancy complications. Treatment with low molecular weight heparin (LMWH) improves pregnancy outcome, but the underlying mechanisms are not clear., Methods of Study: We analyzed Treg frequency in blood from thrombophilic pregnancies treated with LMWH (n = 32) or untreated (n = 33) and from healthy pregnancies (n = 39) at all trimesters. Additionally, we treated pregnant wild-type, heterozygous and homozygous factor-V-Leiden (FVL) mice with LMWH or PBS and determined Treg frequency, pro-/anti-inflammatory cytokine levels and Caspase-3-activity in placenta and decidua., Results: Treg frequencies were increased in second and third trimester in LMWH-treated thrombophilic pregnancies compared to controls. Treg levels were comparable to those of normal pregnancies. Homozygous FVL mice had decreased decidual Tregs compared to wild-type mice. LMWH treatment normalized Tregs and was associated with increased decidual IL-10 mRNA. LMWH diminished Caspase-3-activity in mice of all genotypes., Conclusion: We demonstrated anti-apoptotic and anti-inflammatory effects of LMWH in pregnant FVL mice. LMWH increased Treg levels in mice and humans, which suggests benefits of LMWH treatment for thrombophilic women during pregnancy., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Clinicians sometimes are confronted with the challenge of transfusing haemorrhaging Rhesus (Rh) D negative patients with Rh D positive blood to save their lives. There are concerns about alloimmunization and future haemolytic disease of the newborn in women of the reproductive age. Another fear is transfusion reaction if they receive another Rh D positive blood in future. We present a 32-year-old Rh D negative woman, who had postpartum haemorrhage in her first pregnancy and was transfused with Rh D positive blood because of unavailability of Rh D negative blood. She did not receive anti D immunoglobin but subsequently had a normal term pregnancy of an Rh positive fetus without any detectable anti D antibodies throughout the pregnancy. In life threatening situations from obstetric haemorrhage, transfusion of Rh D negative women with Rh D positive blood should be considered as the last resort.

Recurrent miscarriage is frustrating for the physician and a heartbreaking experience for the patient. Approximately 5% of couples trying to conceive have two consecutive miscarriages. Despite a thorough study of patients, the aetiology of this common obstetric complication is unknown in 50% of cases. Known causes include abnormal chromosomes, endocrinological disorders and uterine abnormalities. Although antiphospholipid antibodies have been demonstrated in miscarriages, the role played by alloimmune mechanisms remains unclear. New immunological approaches such as natural killer cells, regulatory T cells, tumour necrosis factor α, cell-derived microparticles, leptin, certain glycoproteins and cytokines should be considered. The management of thyroid diseases and immunological disorders is continuously evolving. Several genetic diagnostic procedures such as parental karyotyping and preimplantation genetic screening should probably not be used routinely. Antiphopholipid syndrome and some recurrent miscarriage-related endocrinological disorders can be effectively treated. Finally, new therapeutic approaches and the pleiotropic effects of old ones have led to improved fetal-maternal outcomes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: This study aimed to assess fetomaternal hemorrhage (FMH) among RhD negative pregnant mothers using two techniques, Kleihauer-Betke (KBT) and Flow cytometry (FCM). To determine if patient-specific doses of prophylactic anti-D warrant further investigation in Ethiopia and wider Africa., Methods: Hospital- based cross-sectional study was conducted among 75 RhD negative pregnant mothers using convenient sampling technique., Result: FMH has been detected in 52% and 60% by KBT and FCM techniques, respectively. The volume of FMH quantified in the majority of the cases (92.5% and 87%) was <10 mL fetal blood while >30 mL in 1.3% (1/75) and 2.7% (2/75) as calculated by KBT and FCM, respectively. The FMH calculated by the two methods have good correlation; r = 0.828 (p = 0.000) for categorized and r = 0.897 (p = 0.000) for continuous values and the agreement between the FCM and KBT was moderate with kappa (κ) value of 0.53 (p = 0.000)., Conclusion: Most of FMH calculated (<10 mL) could have been neutralized by lower doses which might have lower costs than administering 300 μg dose which is currently in practice in our country for affording mothers. Besides, it also showed that the volume of FMH was >30 mL in 1.3% and 2.7% of the cases as calculated by KBT and FCM, respectively, which need more than 300 μg dose RhIG for neutralization. Further investigation into the cost- effectiveness and scalability of patient- specific dosing of prophylactic anti-D appears warranted.

Unexplained postpartum hemorrhage (PPH) refractory to standard hemostatic measures should trigger a heightened clinical suspicion of an acquired bleeding disorder. When hemostatic medical interventions and surgical procedures fail to control the bleeding, then significant postoperative blood loss, debilitating morbidity, loss of fertility, and death may occur. In the setting of an autoantibody inhibitor to factor VIII (FVIII), control of life-threatening PPH and avoidance of subsequent bleeding episodes depends on a timely and accurate diagnosis, prompt hemostatic treatment and eradication of FVIII inhibitors, and appropriate long-term patient care and management. Acquired postpartum hemophilia due to a FVIII inhibitor is a rare cause of PPH; however, delayed treatment can lead to increased maternal morbidity and mortality. Acquired FVIII inhibitors also pose an emerging bleeding threat to the neonate as a result of possible transplacental transfer of FVIII autoantibodies to the fetus during the last trimester of pregnancy. The purpose of this review is to increase awareness among hematologists and obstetricians/gynecologists regarding the occurrence of FVIII neutralizing autoantibodies as a cause of PPH, and emphasize the importance of collaboration between obstetrician/gynecologists and hematology specialists to optimize the diagnostic evaluation, treatment, and long-term management of women who experience PPH due to an acquired FVIII inhibitor., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Thalassemia Intermedia (TI) has a wide clinical profile with many patients requiring only occasional transfusions. To prevent alloimmunization, we adopted a policy of issuing phenotype matched red blood cells in 2009. We examined transfusion indications and alloimmunization rate in TI patients., Study Design and Methods: Clinical and blood bank records of 37 TI patients were reviewed., Results: 23 Patients required transfusion for pregnancy (26), splenectomy (8) and anemia (11). Since 2009, total of 335 units were transfused with only one antibody developing after transfusing a non-phenotype matched unit., Conclusion: The commonest indication for blood transfusion was pregnancy. Providing phenotype matched blood has successfully reduced the rate of alloimmunization., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A 23-year-old primigravida of North African origin presented with a positive antibody screen at booking at 15 weeks of gestation. An antibody to a high-frequency antigen (HFA) of unknown identity was detected, which was reactive with the red blood cells of the father. This led to several challenges including antibody identification, clinical monitoring to detect signs of haemolytic disease of the foetus and newborn (HDFN) and compatible blood in case perinatal transfusion was needed. Anti-Emm was identified 2 months post-partum. This is the first published case which describes a pregnant patient with anti-Emm., (© 2013 International Society of Blood Transfusion.)

Aim: To compare the rates of gestational diabetes mellitus (GDM) among Thai or other South-East Asian women with increased and normal peripheral white blood cell (WBC) counts in early pregnancy. The risk of GDM in relation to WBC count was also determined., Methods: We included singleton pregnant women who sought their first antenatal care in our institution between May 2010 and December 2011. Subjects were 595 gravidas with an increased WBC count while controls were 595 pregnancies with a normal WBC count. Data of pregnant women were collected. The WBC of each woman was obtained from a complete blood count performed in the first trimester. The rates of GDM between both groups were compared. The odds ratio (OR) with 95% confidence interval (CI) of GDM development in the subject group was determined by multivariate analysis., Results: Data on 570 subjects with increased WBC and 575 controls with normal WBC were obtained. The rate of GDM was significantly higher in subjects compared to controls at 13.2% versus 5.2% (P<0.001) with a crude OR of 2.75 (95% CI, 1.77-4.28). By multivariate analysis, the subject group was found at increased risk of GDM compared to the control group, with an adjusted OR of 2.20 (95% CI, 1.39-3.47)., Conclusion: Thai or other South-East Asian women with an increased WBC count in early pregnancy had a significantly higher rate of GDM than women having a normal WBC count. Our results demonstrate that WBC count is an independent risk factor for GDM., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Background: Several studies have documented the role of antibodies against human platelet (PLT) antigen (HPA)-15 in alloimmune-mediated thrombocytopenia including neonatal alloimmune thrombocytopenia, PLT transfusion refractoriness (PTR), and posttransfusion purpura in Caucasian persons. However, the relevance of anti-HPA-15 in PTR among the Japanese population is still unclear., Study Design and Methods: The sera of 305 multiply PLT transfused (MPT) patients, previously investigated for the presence of human leukocyte antigen (HLA) and HPA antibodies by mixed passive hemagglutination, were reexamined for the presence of HPA-15 alloantibodies, using the monoclonal antibody-specific immobilization of PLT antigens (MAIPA) technique., Results: Among the 305 MPT samples, antibodies against HPA-15 alloantigen was detected in seven (2.3%), two (0.66%) being anti-HPA-15a and five (1.64%) being anti-HPA-15b. Additionally, one case of CD109 panreactive antibody was found (0.33%). Among them, one aplastic anemia patient with blood group O developed multispecific anti-HLA and anti-HPA-15b alloantibody after MPTs. However, transfusion with HLA-matched PLTs of blood group AB did not result in adequate PLT count increment. Analysis of the possible influence of immune anti-A and anti-B by the MAIPA assay resulted negative, indicating that anti-HPA-15b is responsible for the refractory state in this patient., Conclusion: In this study, we found alloimmunization against HPA-15a and -15b in Japanese populations and demonstrated the relevance of these antibodies in a patient with PTR., (© 2013 American Association of Blood Banks.)

Problem: Cytomegalovirus (CMV) infection was previously reported in pregnancy complications. However, its seroprevalence and associated Toll-like receptor (TLR) expression in early-onset preeclampsia (EOPE) with hemolysis, elevated liver enzyme and low platelets syndrome (HELLPs) are unexplored., Method of Study: A case–control study was performed to examine maternal CMV antibodies, neutrophil Toll-like receptor (TLR)-2 and -4 expression as well as the cytokine profile in EOPE with HELLPs (EOPE-HELLPs) (n = 10), late-onset preeclampsia (LOPE) (n = 20), normal pregnancy (n = 60), and non-pregnancy (n = 20) controls., Results: EOPE-HELLPs had significantly increased CMV IgG sero-positivity, upregulated TLR-2/-4 mRNA expression, increased serum IL-6 and TNF-α, and reduced IL-10 compared with matched normal and non-pregnancy controls. No significant difference was observed between LOPE and normal pregnancy controls., Conclusion: We observed a significant association between CMV IgG sero-positivity and innate immune response in EOPE-HELLPs. Our data suggest that CMV infection may be a risk factor for this disorder.

This is a case study of a 23-year-old pregnant Polynesian woman with anti-Jk3 identified in her plasma during her third visit to a hospital. This patient, with a history of mild anemia due to beta-thalassemia minor and two known transfusion of packed red cells came to an emergency room complaining of severe abdominal cramps. Her hemoglobin during her second hospital visit was 7.5 g/dL and her antibody screen was negative. Two units of crossmatch compatible packed cells were transfused with no adverse reaction and she was discharged. Four days post transfusion, she returned to the hospital complaining of back pain and fatigue and she was running a fever (101 degrees F). Her antibody screen was positive, direct antiglobulin testing was also positive and the eluate showed pan-agglutination with a red cell panel. Anti-Jk3 was identified in her plasma by the Red Cross and a delayed transfusion reaction was suspected. As a result, Kidd null crossmatch compatible units were obtained from relatives. The patient was successfully transfused and was discharged with a hemoglobin of 10.1 g/dL. The fetus appeared to be unaffected by the antibody. This case reiterates the hard-to-identify characteristics of Kidd antibodies and highlights the need for medical laboratory personnel to be informed on the prevalence of the Kidd null phenotype among various populations. Educating ethnic populations with rare phenotypes and organizing targeted blood drives may increase inventories of these rare blood phenotypes.

Aim: To estimate the current incidence of maternal sensitisation to Rh(D) and examine reasons for prophylaxis failures., Method: Retrospective chart review of new sensitisations to Rh(D) detected in antenatal records, between 2005 and 2012 in Christchurch, New Zealand and systematic examination of circumstances likely to have caused prophylaxis failures., Results: Fifty-four new sensitisations in an at-risk population of about 4624 in 8 years means an incidence of roughly 1.1%. In 86.6% of 45 sensitisations where information was available, there was a recognised sensitising event including previous deliveries while in 13.3% there were none. Of those with recognised sensitising events, 46.1% had anti-D prophylaxis per local guidelines, in 12.8%, prophylaxis was given though it did not conform, entirely, to guideline. No prophylaxis at all was given to 41% despite a sensitising event being recognised., Conclusion: The incidence of maternal sensitisation to Rh(D) in Christchurch, New Zealand, is as expected given our prophylaxis regimen. Half the sensitisations were associated with complete or partial failure to follow local guidelines. Better adherence to this may reduce incidence of sensitisation. It is also thrice as high as might be expected with a routine antenatal anti-D prophylaxis (RAADP) program. An economic analysis of RAADP in New Zealand will be useful.

Objective: Recent studies have implicated hepatitis C virus (HCV) in the pathogenesis of immune thrombocytopenia. In pregnancy-associated immune thrombocytopenia, multidisciplinary management is required due to a potential for bleeding complications. We performed a retrospective review of HCV-infected pregnant women and age-matched controls who were not infected with HCV., Methods: One hundred and six women with a HCV viral load were identified from 2009 to 2011., Results: Thrombocytopenia was identified in 10.3% of HCV-infected pregnant women and 1.6% of age-matched controls (P<0.001). Mean platelet count during pregnancy was 120 ± 23 × 109/L in HCV-infected women and at delivery was significantly lower in HCV-infected women than in controls (P=0.01). Despite the significant difference in platelet counts, there was no significant difference in estimated blood loss (EBL) at delivery. Regional anaesthesia was performed in 73% of thrombocytopenic HCV-infected women and no complications were recorded. There were no fetal bleeding complications., Conclusion: In the first study to date to investigate the impact of HCV on maternal platelet count we demonstrated a significantly higher frequency of thrombocytopenia and a significantly lower platelet count in HCV-infected pregnant women compared with controls. Interestingly, thrombocytopenia had no detectable impact on EBL at delivery.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the association of antiphospholipid antibodies (aPL) with thrombosis and/or pregnancy loss: classification criteria were defined in the updated international consensus held in Sidney in 2005. Vascular and obstetric manifestations display partially different pathogenetic mechanisms. Thrombosis develop as a result of local procoagulative changes upon triggers influence (second-hit theory). Pregnancy morbidity is thought to be dependent on placental thrombosis and complement activation. The laboratory tests include Lupus Anticoagulant (LA), a functional assay, and anticardiolipin (aCL) and anti-β2-glycoprotein I antibodies detected by solid phase enzyme-linked immunosorbent assay (ELISA). The LA testing is relatively standardized while there's still significant interlaboratory discrepancy in ELISA tests. Current APS criteria are under discussion: since for vascular and obstetric APS, different pathogenetic mechanisms have been shown, some criteria variation could also be contemplated. What is the weight of aPL antibodies in provoking thrombosis and which contribution could be expected from aPL per se is debated. As thrombosis is generally considered to be multi-factorial, each case needs a risk-stratified approach. Any primary prophylaxis, intensity and duration of secondary prophylaxis should take into account aPL profile, other cardiovascular risk factors and systemic autoimmune diseases associated. We look forward to the publication of recommendations of the leading experts in the field, developed during the recent 14th International Congress in Rio de Janeiro, Brazil.

Unlabelled: Recurrent miscarriage occurs in 1-5% of women at reproductive age. The most common cause of recurrent miscarriage is chromosomal abnormalities of the embryo (41%), chromosomal aberrations parents (10%), anatomical abnormalities of the uterus (5%), infectious and hormonal factors. In about 25% of women, no cause of recurrent miscarriage is usually found. Therefore it seems important to study all factors possibly inducing pregnancy disorders., Objective: The aim of this study was to find a difference in serum protein fractions between women with primary and secondary recurrent miscarriage., Methods: The study group consisted of 52 women (aged 36.0 +/- 4.9) with recurrent miscarriage. Nine of them (17%) reported one earlier regular pregnancy ending with childbirth without complications. Control group comprised 30 non-pregnant women (aged 36.1 +/- 3.6), who had given vaginal birth to healthy children at least twice. Serum protein fractions were separated by electrophoresis in the SDS PAGE buffer system using a Mini PROTEAN 3 cell device. BioRad SDS PAGE Molecular Weight Standards covering mass range of 6.5-200 kDa were used as a reference. Gels were stained with Coomassie Blue R 250 solution. BioRad QuantityOne software was used for the assessment of molecular weight of each protein fraction., Results: Electrophoretic separation revealed 39 protein fractions of 10,243 kDa. Particularly interesting was a 38 kDa fraction present exclusively in serum of women with recurrent pregnancy who had never given birth. Another fraction (74 kDa), not detected in the control group, was found in all women with recurrent pregnancy loss. Protein fractions of 76 and 151 kDa were present only in the control group., Conclusions: The presence of the protein fractions of low- or mid-weight in serum from women with recurrent miscarriage may potentially play a role in the pathomechanism of this disorder

Background and Objectives: Pregnant women with Idiopathic thrombocytopenic purpura (ITP) can deliver neonates with severe thrombocytopenia. Clear evidence declaring the pathophysiological cause of this neonatal thrombocytopenia is lacking, as antiplatelet antibodies are not always detectable in maternal serum. Severe neonatal thrombocytopenia below 50 × 10(9) /l is reported in 8-13% of the neonates from mothers with ITP and intracranial haemorrhage (ICH) in 0-2·9%. Evidence about the optimal postnatal treatment is scarce. Our objective was to evaluate the outcome and management in neonates with passive ITP., Materials and Methods: All neonates from mothers with ITP born between 1980 and 2011 were included. Platelet counts during the first 10 days, presence of ICH and postnatal treatment were recorded. Maternal characteristics were analysed as possible risk factors for severe neonatal thrombocytopenia., Results: Sixty-seven neonates were included. Severe thrombocytopenia (<50 × 10(9) /l) occurred in 20/67 (29·9%) neonates. In three neonates, platelet count rose spontaneously, 18 neonates were treated (one with persistent moderate thrombocytopenia) with the following: platelet transfusions (3), prednisone (2), intravenous immunoglobulin (IVIG) (1), platelet transfusions and IVIG (11), platelet transfusion and prednisone (1). Recurrence of low platelet counts after transfusions was commonly seen. Risk factors for severe neonatal thrombocytopenia were a previous sibling with severe thrombocytopenia and low maternal platelet nadir during pregnancy., Conclusion: In this cohort, severe neonatal thrombocytopenia occurs more frequently than previously reported. To maintain a platelet count above 50 × 10(9) /l, often multiple transfusions and IVIG are required. Multiple transfusions may be avoided by starting IVIG, when platelet count falls below 50 × 10(9) /l after the first platelet transfusion., (© 2013 International Society of Blood Transfusion.)

APS is an autoimmune disease that leads to arterial and/or venous thrombosis, recurrent pregnancy loss and persistently positive aPLs. Patients with clinical manifestations highly suggestive of APS but persistently negative conventional aPLs are classified as having seronegative APS. Ongoing research has revealed the existence of non-criteria antibodies proposed to be relevant to APS and that can be potentially included in the disease's classification criteria. We present a literature review on the most promising antibodies of this heterogeneous aPL family, which includes antibodies to a zwitterionic phospholipid, namely phosphatidylethanolamine, phospholipid-binding plasma proteins, phospholipid-protein complexes and anionic phospholipids other than cardiolipin. Although these molecules can increase the diagnostic yield of APS, their clinical relevance is still debatable and needs to be confirmed by interlaboratory efforts toward standardizing diagnostic tools, in addition to experimental data and larger longitudinal studies.

Protein Z (PZ) is a vitamin K-dependent factor characterized by its homology to other vitamin K-dependent factors (factors VII, IX, and X, protein C and protein S), but lacks any enzymatic activity. Instead, PZ acts as a cofactor for the inhibition of factor Xa through the serpin PZ-dependent protease inhibitor (ZPI). PZ deficiency is associated with a procoagulant state, highlighted by excessive FXa secretion and thrombin production, and is linked with several thrombotic disorders, including arterial vascular and venous thromboembolic diseases. A role for the PZ-ZPI complex in the regulation of physiological pregnancy has been demonstrated, highlighted by the progressive elevation in PZ levels in the first trimester of gestation, which then steadily decline toward delivery. An association between altered plasma PZ concentrations and adverse pregnancy outcomes (recurrent miscarriage, stillbirth, preeclampsia, intrauterine growth restriction, and placental abruption) has been reported. The mechanism by which PZ deficiency leads to adverse pregnancy outcomes is not clear, but it is multifactorial. It may be attributed to the anti-PZ IgG and IgM autoantibodies, which apparently act independently of classical antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I antibodies). PZ deficiency has also been reported to be constitutional, and a number of variants in the PROZ (PZ) gene and SERPINA10 (ZPI) gene are linked with specific adverse pregnancy complications. This review summarizes the relationship between adverse pregnancy outcomes and acquired and constitutional PZ-ZPI deficiency, in order to understand whether or not PZ deficiency could be considered as a risk factor for poor pregnancy outcomes.

A 25-year-old woman was admitted because of proteinuria. A renal biopsy showed mesangial/endocapillary proliferative glomerulonephritis with IgG2-κ deposits. Electron microscopy showed immune complex-type deposits. She also had Coombs-positive hemolytic anemia, anticardiolipin antibodies, and antinuclear antibodies. Middle-dose steroid therapy led to improvement of proteinuria and hemolytic anemia. Six years later, she developed crescentic glomerulonephritis with IgG2-κ deposits during pregnancy. Middle-dose steroid therapy improved renal dysfunction. This is an exceptional case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a recently described rare dysproteinemia-related glomerulonephritis, associated with autoimmune disease. This case also suggests that crescentic glomerulonephritis can be superimposed on PGNMID.

Acquired haemophilia A (AHA) is a potentially life-threatening bleeding disorder occurring in patients without a previous personal or family history of bleeding. Development of immune-mediated autoantibodies against coagulation factor VIII is associated with a wide range of clinical disorders including pregnancy, autoimmune disorders, malignancy, or with no apparent disease. There exists great potential for morbidity and mortality related to acute and recurrent bleeding episodes, making prompt diagnosis and treatment necessary. The two primary goals of treatment focus on cessation of bleeding and eradication of the acquired factor VIII inhibitor. No randomized clinical trials have been conducted regarding treatment, so expert clinical opinion guides therapeutic intervention. This current report provides a profile of patient characteristics, an algorithm for diagnosis, and outlines treatment recommendations based upon current guidelines and clinical experience. As first-line interventions for acute bleeding and inhibitor eradication are generally accepted, we will emphasize discussion of second-line therapeutic options., (© 2013 Blackwell Publishing Ltd.)

The antiphospholipid syndrome (APS) is defined by venous or arterial thrombosis and/or pregnancy morbidity in patients with persistent presence of antiphospholipid antibodies (aPLs). Catastrophic APS is the most severe form of APS, which is associated with rapid development of microvascular thrombosis resulting in multiorgan failure in patients with aPLs. Patients with APS and catastrophic APS are recognized to have a high risk of recurrent thrombosis that can occur despite anticoagulant therapy. Although antithrombotic therapy remains the mainstay of treatment, bleeding manifestations can complicate management and contribute to increased morbidity. Patients with persistently elevated aPL levels, particularly those who exhibit positive testing for lupus anticoagulant, anticardiolipin antibodies, and anti-β2GPI antibodies (triple positivity), appear to be at increased risk for thrombosis and pregnancy complications, whereas isolated positivity for aPLs appears to be associated with low risk. Recognizing that patients with APS have different thrombotic risk profiles may assist clinicians in assessing the risks and benefits of anticoagulation. The optimal type, intensity, and duration of anticoagulation in the treatment of APS remain controversial, particularly for arterial thrombosis and recurrent thrombosis. Future studies that delineate thrombotic risk in APS and evaluate current and novel anticoagulants as well as nonanticoagulant therapies are required.

Background and Objectives: The Colton blood group antigens are carried by the AQP1 water channel. AQP1(-/-) individuals, also known as Colton-null since they express no Colton antigens, do not suffer any apparent clinical consequence but may develop a clinically significant alloantibody (anti-CO3) induced by transfusion or pregnancy. Identification and transfusion support of Colton-null patients are highly challenging, not only due to the extreme rarity of this phenotype, the lack of appropriate reagents in most laboratories, as well as the possibility of confusing it with the recently described CO:-1,-2,3,-4 phenotype where AQP1 is present. This study investigated a new Colton-null case and evaluated three commercially available anti-AQP1s to identify Colton-null red blood cell samples., Methods: The Colton-null phenotype was investigated by standard serological techniques, AQP1 sequencing, immunoblot and flow cytometry analyses., Results: We identified and characterized the Colton-null phenotype in a Gypsy woman who developed an anti-CO3 during her first pregnancy. After developing a simple and robust method to sequence AQP1, we showed that she was apparently homozygous for a new AQP1 null allele, AQP1 601delG, whose product is not expressed in her red blood cells. We also established the Colton specificity of three commercially available anti-AQP1s in immunoblot and/or flow cytometry analyses., Conclusion: This Gypsy woman represents the sixth Colton-null case characterized at the serological, genetic and biochemical levels. The validation here of new reagents and methods should facilitate the identification of Colton-null individuals., (© 2012 The Author(s). Vox Sanguinis © 2012 International Society of Blood Transfusion.)

Study Objective: The quality measure "Rh immunoglobulin administration for Rh-negative women at risk for fetal blood exposure" was recently endorsed by the National Quality Forum. No published data have shown a related performance gap in US emergency departments (EDs). We determine performance in a US ED for appropriate Rh testing and treatment among pregnant ED patients at risk of fetal blood exposure., Methods: This was a retrospective, observational study in an urban, academic ED with 97,000 annual visits. We performed record review of all pregnant ED patients aged 14 to 50 years and presenting between June 1, 2009, and June 1, 2010, to determine whether a sensitizing event or a potential sensitizing event occurred and whether Rh testing and treatment with Rh immunoglobulin were performed when indicated. Performance rates were calculated under 2 different assumptions for patients without Rh testing ordered in the ED but who had previous data in the electronic medical record: (1) unless explicitly documented by the treating physician, previous Rh data were considered as not having been checked; and (2) when available in the electronic medical record, Rh status was always considered as having been checked. Interrater reliability was assessed for whether a trauma represented a sensitizing event., Results: Among 1,465 patients identified, 808 met inclusion criteria; 560 had a sensitizing event and 248 had a potential sensitizing event. Interrater reliability for determination of sensitizing event or potential sensitizing event in trauma was moderate (κ=0.42). Performance rates for Rh testing among patients with sensitizing events, with potential sensitizing events, and overall were 73% (95% confidence interval [CI] 69% to 76%) (408/560), 36% (95% CI 31% to 43%) (90/248), and 62% (95% CI 58% to 65%) (498/808). Appropriate treatment for patients with a sensitizing event, with a potential sensitizing event, and overall was 56% (95% CI 39% to 71%) (19/34), 0% (95% CI 0% to 49%) (0/5), and 48% (95% CI 33% to 63%) (19/39). Assuming that physicians were aware of previous Rh results yielded performance rates of 96% (95% CI 93% to 97%) (535/560), 73% (95% CI 67% to 78%) (181/248), and 89% (95% CI 86% to 91%) (716/808) and treatment performance rates of 54% (95% CI 38% to 69%) (20/37), 0% (95% CI 0% to 30%) (0/11), and 42% (95% CI 29% to 56%) (20/48)., Conclusion: In this single-center study, among patients with a sensitizing event, performance was moderate for Rh testing and treatment with Rh immunoglobulin. Despite lack of consensus or uncertainties in certain measure definitions, in at least 1 US academic ED there appears to be an opportunity for further evaluation and performance improvement in this area., (Copyright © 2011 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

The antiphospholipid syndrome is characterized by recurrent thrombosis and pregnancy morbidity in association with the persistent presence of autoantibodies called antiphospholipid antibodies. Antiphospholipids are a heterogeneous group of circulating autoantibodies associated with a risk of thrombosis and can paradoxically prolong in vitro the clotting times. In the past few years, significant improvement has been made in understanding the pathophysiologic mechanisms of the disease, thus raising the possibility of future predictive test for the risk of thrombosis. The aim of this review is to make an overview on how the antiphospholipids increase the risk of thrombosis and to provide an update of the laboratory diagnosis and the possible future therapies., (Copyright © 2011 Société nationale Française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Background: Analysis of reticulated platelets (RP), the youngest form of platelets in peripheral blood, is useful for assessment of thrombopoietic response in thrombocytopenic conditions due to intense immunological platelet destruction., Aim: The aim of the study was to assess the value of RP measurement for differentiation between pregnancy-related thrombocytopenia (PT), immunological thrombocytopenia (IM) and hereditary thrombocytopenia (HT) in pregnant women with platelet count below 100 G/L., Material: The study included 49 pregnant thrombocytopenia women (21 with PT, 22 with IM, 6 with HR) as well as 22 healthy pregnant women (Control)., Methods: The percentage of RP in peripheral blood was measured using double staining with: PE-labeled anti CD41 (Dako) and thiazole orange (Beckton Dickinson). The measurements were performed several times during pregnancy (II and III trimester) and delivery. Anti-platelet antibodies were tested by immunofluorescence and immunoensimatic assays. HPA1a antigen was determined by PCR/SSP., Results: The average platelet count in all groups of thrombocytopenia women was significantly lower than in control group. The mean RP percentage in the control group (5.31%) was within the range of the haematological normal value (0.5-6%), and for thrombocytopenia women it was: 9.19% for PT women, 14.75% for IM women and 14.94% for HT women and was significantly higher than that in the control group. In the group of IM pregnant women the RP percentage was significantly higher in the II trimester than in the PT women. Anti-platelet antibody and HPA1a antigen testing excluded alloimmunological/fetus/neonatal thrombocytopenia in the study material., Conclusion: RP analysis has been proved useful for preliminary differentiation of PT and IT in the II trimester of pregnancy. Higher RP percentage informs the physician of the likelihood of immunological thrombocytopenia in the pregnant woman as well as of the delivery of a thrombocytopenia child.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the occurrence of thrombotic or obstetrical events associated with the presence in the serum of patients of antibodies that are associated with thrombosis. For the diagnosis of APS, the presence of either lupus anticoagulant, anticardiolipin or anti-β2-glycoprotein1 antibodies of IgG or IgM isotype is required through laboratory testing. Other autoantibodies such as antiphosphatidylethanolamin or antiphosphatidylserin/prothrombin complex antibodies may be interesting in the diagnosis of APS when common antiphospholipid antibodies are missing. These autoantibodies are still under evaluation for their diagnostic contribution. Despite numerous attempts, the assays that are available for the identification of antiphospholipid antibodies have not been standardized yet, which leads to high variability between reagents and laboratories. Thus, to optimize the biological monitoring of APS syndromes, it is mandatory to have consecutive samples analyzed in the same laboratory., (Copyright © 2011. Published by Elsevier SAS.)

Objective: Antiphospholipid antibodies (aPL) associated with thrombembolic events and/or pregnancy morbidity characterize the so-called antiphospholipid syndrome (APS). Beta2glycoprotein I (β2GPI) represents the major target antigen for aPL, but the pathogenic role of anti-β2GPI antibodies (aβ2GPI) is still unclear. Some authors assume they play a role in activating platelets. The effects of aβ2GPI antibodies on platelet P-selectin expression were evaluated in this study., Methods: Aβ2GPI antibodies in the plasma of a pregnant APS patient were isolated by affinity chromatography during two different stages (catastrophic and quiescent) of the disease. Gel filtered platelets (100,000/μl) from healthy volunteers were incubated with β2-GPI (20 μg/ml) and with different concentrations (5, 25 e 50 μg/ml) of aβ2GPI antibodies. P-selectin surface expression on platelets was assessed by flow cytometry using a specific fluorescent antibody directed against P-selectin., Results: Aβ2GPI antibodies induced platelet activation only in the presence of thrombin receptor activator for peptide 6 (TRAP-6), a platelet agonist, at a subthreshold concentration. Aβ2GPI antibody enhancement on platelet surface P-selectin expression was stronger in the catastrophic than in the quiescent phase of the disease (47% versus 15%)., Conclusions: TRAP-6 dependent platelet activation by aβ2GPI antibodies is consistent with the “two hit” pathogenetic hypothesis for thrombosis. Aβ2GPI antibodies induce higher platelet P-selectin expression during the active rather than in the acute phases.

Spontaneous pregnancy loss is often associated with aberrant maternal inflammation and systemic coagulopathies. However, the role of inflammation in the development of obstetric coagulopathies is poorly understood. Further, questions remain as to whether systemic coagulopathies are linked to placental haemostatic alterations, and whether these local alterations contribute to a negative foetal outcome. Using a model of spontaneous foetal loss in which pregnant rats are given a single injection of bacterial lipopolysaccharide (LPS), we characterised the systemic maternal coagulation status following LPS administration using thromboelastography (TEG), a global haemostatic assay that measures the kinetics of clot formation. Systemic maternal coagulopathy was evident in 82% of LPS-treated rats. Specifically, we observed stage-I, -II, and -III disseminated intravascular coagulation (DIC) and hypercoagulability. Modulation of inflammation through inhibition of tumour necrosis factor α with etanercept resulted in a 62% reduction in the proportion of rats exhibiting coagulopathy. Moreover, inflammation-induced systemic coagulopathies were associated with placental haemostatic alterations, which included increased intravascular, decidual, and labyrinth fibrin deposition in cases of DIC-I and hypercoagulability, and an almost complete absence of fibrin deposition in cases of DIC-III. Furthermore, systemic and placental haemostatic alterations were associated with impaired utero-placental haemodynamics, and inhibition of these haemostatic alterations by etanercept was associated with maintenance of utero-placental haemodynamics. These findings indicate that modulation of maternal inflammation may be useful in the prevention of coagulopathies associated with complications of pregnancy.