Search

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.)

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.)

First trimester recurrent fetal loss and severe second or third trimester placental vascular disorders are still frequently unexplained. Acquired biological thrombophilia (antiphospholipid syndrome, essential thrombocythemia) are known risk factors. Genetic thrombophilia may represent a new risk factor for placental vascular diseases, but reported data are conflicting. Combined hereditary thrombophilias are indeed a moderate risk factor, but even in these cases most pregnancies are normal giving healthy live birth children. Whether hereditary thrombophilia is associated with recurrent severe placental vascular disorders is unknown.

An autologous blood donation with cryopreservation in a pregnant woman with natural antibody against a high frequency alloantigen is reported. A natural anti Gerbich antibody and a rare erythrocyte phenotype at high risk of polyimmunization was discovered during the third month of pregnancy. This leads to recommend the constitution of an autologous blood reserve. Before first sampling a moderate iron deficiency anaemia (10.3 g.dL-1) was treated with 600 mg of intravenous iron sucrose. Four blood packs of 350 mL were taken; after every sampling 200 mg of iron sucrose were injected intravenously. No maternal or foetal adverse effects occurred. Five weeks before delivery, an autologous blood reserve consisting in 4 cryopreserved red cells packs and 4 fresh frozen plasma was constituted. Epidural analgesia was used for delivery. No haemorrhage occurred. The reserve was not used and remained available for future use (one year for fresh frozen plasma and without limit for red cells).

The diagnosis of fetomaternal alloimmune thrombocytopenia (FMAT) was made in a newborn with thrombocytopenia and intracranial hemorrhage. The first child of the family was severely affected with neurodevelopmental sequelae secondary to intracranial hemorrhage. According to the maternal HPA phenotype, close to 100% of subsequent pregnancies could be expected to be affected as the homozygous state was observed in both platelet systems. Another infant was born after a poorly followed pregnancy and was affected as was his elder brother. Prednisolone was given during another pregnancy. A thrombocytic newborn without intracranial hemorrhage was delivered by prudent cesarian section. The infant received platelet transfusion (maternal platelets). We present case histories of FMAT, and stress the conditions for prenatal diagnosis and management.

Introduction: Red cell autoantibodies are very rarely observed in pregnant women. We report one case related to the presence of a lupus anticoagulant., Exegesis: A 32-year-old woman had a history of two intrauterine deaths that had occurred at weeks 32 and 33, respectively. Due to the presence of a lupus anticoagulant, prednisone (20 mg/day) and subcutaneous calcium heparin were administered during her third pregnancy. The direct antiglobulin test remained positive throughout the pregnancy; however, hemolysis could not be detected. Caesarean section was done in emergency at week 29, due to fetal bradycardia related to severe fetal hemolysis., Conclusion: When autoimmune hemolysis occurs during pregnancy, risks for the fetus increase with the severity of hemolysis in the mother. It is thought that child mortality reflects the existence of anemia, rather than the existence of hemolysis. Our observation suggests that severe fetal hemolysis may occur, despite the absence of hemolysis in the mother.

Autoimmune hemolytic anemias (AIHA) are characterized by hyperhemolysis associated with the presence of the immunoglobulins IgG, IgM or IgA on the red cell membrane. These immunoglobulins react as auto-antibodies against the red cell auto-antigens of the patient. The diagnosis is supported by clinical and biological signs of hemolysis, and by the identification of the auto-antibodies using the direct antiglobulin test (DAT). Here we report 14 cases of patients who showed the clinical and biological profile of AIHA, but who gave a negative DAT. We therefore tried to determine the presence of IgA on the red cell membrane with a method more sensitive than the DAT: the gel test using anti-IgA. With such a gel test, we demonstrated that there were IgA auto-antibodies on the red cell membrane in the 14 cases, therefore confirming the diagnosis of AIHA. We discuss the interest of performing a gel test with anti-IgA in each case where AIHA is suspected, but in which a negative DAT has been observed.

Background: Neonatal alloimmune thrombocytopenia (NAIT) in the HPA-3a system is responsible for less than 5% of all cases of NAIT., Case Report: Thomas, a male infant, was born at 39 weeks of gestation after an uncomplicated pregnancy. Delivery was normal. The Apgar score was 9 at 1 minute, and 10 at 5 and 10 minutes. At 1 hour of age, he displayed extensive petechiae and purpura over the back. The platelet count was 8,000/mm3. Hematesis and extensive petechiae were noted, leading to an exchange transfusion followed by a transfusion of 0.5 U/kg of random donor platelets, 0.4 g/kg/d of intravenous immunoglobulin (IVIg) and 10 mg/kg/d of corticosteroids. IVIg were discontinued on d5 and corticosteroids on d10. There was no relapse of thrombocytopenia. A neonatal alloimmune thrombocytopenia with an HPA-3a (Baka) incompatibility was confirmed., Conclusion: HPA-3a incompatibility is certainly more frequent than the rare cases reported and must be searched for in all cases of neonatal thrombocytopenia.

During the neonatal period, 6 infants born to mothers with auto-immune thrombocytopenia purpura were diagnosed as having severe thrombopenia (platelet counts below 30 X 10(9)/l). High doses of intravenous immunoglobulins (IVIG) (0.4 g/kg/injection for 2 infants and 1 g/kg/injection for 4 infants) were administered as of the first week of life. Short-term efficacy was good in all cases (platelet counts over 50 X 10(9)/l, 2-10 days after the first injection). During the second week of life, 5 newborns had relapses which were rapidly reversed by one or several IVIG injections. The thrombopenia was cured between days 19 (shortest) and 41 (longest) and, more over, no side effects were observed. High doses of IVIG seem to be an effective and well-tolerated treatment for neonatal auto-immune thrombopenia, and they can be recommended over classical treatments (corticotherapy, exchange transfusion, platelet transfusion) as a first line of attack.

The authors describe 6 cases of pregnancy, four of the patients presenting fetomaternal Rhesus incompatibility, and two showing no abnormality. Fetal heart rhythm (FHR) recordings in all patients demonstrated the presence of a sinusoidal rhythm, either alone or associated with deceleration. The physiopathology of the rhythm, according to a very critical analysis of reports in the published literature (very severe fetal anemia, hypoxia), was not typical in three of the cases. The authors conclude that the observation of this sinusoidal rhythm for a period of up to 60 min, but not repeated, does not constitute a danger for the fetus. If the period is longer, however, or if there is a fetomaternal pathological condition, decelerations, or reduced amplitude of FHR oscillations, there is a very severe risk to the fetus and the need for urgent delivery has to be seriously considered.

Many pregnant women with AITP bear children with transient thrombocytopenia which is a potentially life threatening complication. Previous reports have demonstrated that monitoring of IgG circulating platelet antibodies may help with the management of these women. We report the case of a pregnant woman with AITP whose sera contained an IgG auto antiplatelet demonstrated by the fluorescein labelled antiglobulin techniques. Steroids had a beneficial effect with a return to a normal of the mother's platelet count but with no disappearance of the circulating antibody. Surprisingly the neonatal platelet count was normal and studies in the baby showed that the antibody had not crossed the placenta in detectable amounts. This case demonstrates our current inability to predict fetal thrombocytopenia and plan the mode of delivery.

High dose gammaglobulin therapy for pregnant women with idiopathic thrombocytopenic purpura may be suitable for both mother and foetus during pregnancy. A newborn with severe thrombocytopenia secondary to maternal illness, was treated successfully by intravenous gammaglobulin, without toxicity. In such a case, we believe the platelet count is not the only criterion for starting immunoglobulin therapy.

Rhesus factor immunisation and its complications should disappear if the indications and the techniques for abolishing it are followed. The indications follow from the usual mechanism by which immunisation occurs. This is the passage of Rh positive fetal red blood cells into the maternal circulation where they are detected by Kleihauer's test. If in pregnancy uterine bleeding, of accidental trauma occur or if amniocentesis, versions, operations on the pregnant uterus are performed or intrauterine death occurs, the necessary preventive action has to be performed on a rhesus negative woman. When pregnancy comes to an end, be it because of delivery at term when every rhesus negative woman who has not been immunised has to be treated (if the infant is rhesus positive) so the same applies after spontaneous abortion, extra-uterine pregnancy and especially after therapeutic termination of pregnancy after which it is often forgotten. The technique is simple: Within 72 hours a dose of 85 micrograms of anti D globulin is enough if injected intravenously or intramuscularly. Sometimes this quantity has to be increased, however, when the Kleihauer test has shown that more than 5 ml of rhesus positive blood has passed into the maternal circulation, or if blood of the wrong group has been transfused. The dose to neutralise 1 ml of blood is 10 micrograms.

Immune thrombocytopenic purpura can no longer be considered as incompatible with pregnancy provided that close surveillance is undertaken. However, the main risk (a possible intracranial hemorrhage) persists in the newborn when severe thrombocytopenia due to the placental transfer of maternal IgG has occurred. None of the maternal parameters is predictive of the fetal thrombocytopenia or of its magnitude. A platelet count on fetal blood obtained by in utero or scalp sampling allows the choice between vaginal delivery or cesarean section, to limit the risk of intracranial bleeding. In most cases i.v. IgG infusion allows rapid correction of severe thrombocytopenia in the newborn.

The analysis of 669 levels of maternal serum alpha-fetoproteins carried out using a radio-immunological technique with double antibodies has enabled a diagram of normal values to be established on the one hand has shown up certain modifications of levels when different pathological conditions arise in pregnancy on the other hand. Raised levels were found in: intra-uterine fetal death. In some cases the rise preceded death, in twin pregnancies. Low levels were found in: severe pre-eclamptic pregnancies, in low intra-uterine fetal growth after the 32nd week, in threatened premature labour. Finally, the levels of AFP in the maternal serum were found to be normal in two cases where there were neural tube malformations. The existence of variations in the levels of AFP in maternal serum in a variety of pathological features suggests that these levels could be used as a new parameter in the biochemical monitoring of the fetus.