Inherited thrombotic thrombocytopenic purpura in pregnancy.

OBJECTIVE: The primary pathologic reason for thrombotic thrombocytopenic purpura (TTP) lies in the systemic formation of platelet aggregations in association with endothelial cells damage. Endothelial damage is a result of an abnormal synthesis and metabolism of unusually large von Willebrand Factor (ULvWF) multimers. In normal conditions vWF cleaving metalloprotease, known as ADAMTS-13 (A Disintegrin And Metalloproteinase with Thrombospondin type-1 motif, member 13) prevents the ULvWF entrance in the circulation. It already has been proven that thrombotic thrombocytopenic purpura is strongly correlated with severe congenital or acquired deficiency of ADAMTS-13. Congenital ADAMTS-13 deficiency is known as Upshaw-Schulman Syndrome and it accounts for only 2-4% of all TTP cases. It is conditioned by genetic variants of the ADAMTS-13 gene causing reduced ADAMTS-13 synthesis and shows an autosomal recessive type of inheritance. CASE PRESENTATION: We present an interesting case of a 20 year old patient, primigravida, nulliparous, in 28th gestational week of twin pregnancy with undiagnosed Upshaw-Schulman Syndrome. The patient was transferred from the district hospital to the Tertiary Perinatal Care Center because of thrombocytopenia and suspicion of hemolytic-uremic syndrome. Genetic analysis performed 5 years after patient's death (before 2008 that kind of genetic analysis had not been available in Poland) showed a homozygotic mutation in the ADMTS13 gene (4143insA) which confirmed the diagnosis of Upshaw-Schulman Syndrome. CONCLUSIONS: 1. TTP, especially hereditary Upshaw-Schulman Syndrome, is extremely rare and complicates the course of pregnancy. It is usually very sudden and dramatic; 2. Differential diagnosis of this disease is difficult and treatment strategy very burdensome for the patient. For this reason, diagnosis of micro-angiopathic disorders need to be simultaneously based on both clinical symptoms and laboratory findings; 3. Genetic diagnosis that confirms exact recognition of Upshaw-Schulman Syndrome is not commonly available; 4. The described case was a huge diagnostic challenge, and actually the final diagnosis was published until five years after the patient's death. Before 2008, that type of genetic analysis had not been available in Poland; 5. Despite the enormous progress in medical knowledge and experience, the exact diagnosis of TTP, including Upshaw-Schulman Syndrome, of this condition remains very difficult.

Recommendations for the management of trauma or surgery-related massive blood loss.

UNLABELLED: Exsanguination is an underestimated cause of treatment failures in patients with severe trauma or undergoing surgery. In some patients the primary dysfunction of blood clot formation is a direct cause of a massive blood loss. Patients without previous coagulation disorders are at risk of coagulopathy following intraoperative or post-traumatic bleeding, where the local haemostasis does not warrant bleeding cessation. THE AIM OF THE STUDY: was to assess the therapeutic value of various components of a complex interdisciplinary approach, based on the opinion of the experts treating patients with massive bleeding. MATERIAL AND METHODS: The study was conducted by anonymous questionnaire, using the analogue representation of the argument strength. The results were analyzed based on the techniques of descriptive statistics. The argument was considered a key parameter, when the median value of strength was located in the highest quartile. RESULTS: It was found that the arguments of the highest strength for the risk of developing the posthaemorrhagic coagulation disorders are: loss of more than one third of blood volume, fluid therapy in an amount greater than 35 ml/kg, administration of more than 5 units of packed red blood cells, insufficient supply of fresh frozen plasma and platelets in proportion to packed red blood cells, severe acidosis and hypothermia. The most important tests for post-haemorrhage coagulopathy are: anatomically non-localized bleed, abnormal values of the standard coagulation parameters and fibrinogen level below 1 g/L. In the treatment of post-haemorrhagic coagulopathy the team of experts pointed out the benefits of antifibrinolytic drugs, concentrates of prothrombin complex and recombinant activated coagulation factor VII. CONCLUSIONS: Multidisciplinary therapeutic management of bleeding patients is associated with employment of appropriate treatment methods to achieve the best possible outcome. Factors influencing the development of coagulopathy, the methods of diagnosis and proposed techniques of treatment may facilitate therapeutic decisions in bleeding patients requiring massive transfusion of blood components.

[Is venous thrombembolism during pregnancy an indication for routine assay of antithrombin activity and antithrombin supplementation?]. / Czy zylna choroba zakrzepowo-zatorowa w przebiegu ciazy stanowi wskazanie do rutynowego oznaczania i uzupelniania niedoboru antytrombiny?

During pregnancy the concentrations of many coagulation factors are increased what leads to a "physiological" hypercoagulability status and constitutes a natural protection against delivery hemorrhage. These changes may be conducive to venous thrombembolism. Antithrombin is one of the endogenous clotting inhibitors. As a serine protease, it inactivates thrombin and the efficiency of this reaction is intensified by heparin. Acquired antithrombin deficiency is caused by disseminated intravascular coagulation syndrome, deep vein thrombosis, neoplasms, nephritic syndrome, renal failure, liver diseases, long-term estrogen treatment, dialysis or extracorporeal circulation. There are also cases of inherited antithrombin deficiency which leads to thrombophilia. The following study presents a course of pregnancy and postpartum of a woman with deep vein thrombosis and acquired antithrombin deficiency as well as the applied treatment. The legitimacy of routine assay of antithrombin activity and antithrombin supplementation in pregnant women with thrombosis was considered. This procedure may be helpful when dealing with obese pregnant patients as it is difficulty to identify and establish a therapeutic dose of heparin in their cases. Therapy guidelines for pregnant patients with thrombosis and acquired antithrombin deficiency have not been established yet.

[Future of prenatal cytogenetic studies: rapid aneuploidy testing or full karyotype]. / Zasady postepowania oraz stosowanie profilaktyki przeciwzakrzepowej u ciezarnych z powiklaniami polozniczymi oraz trombofilia wrodzona.

Thrombophilia is a congenital or acquired disorder of haemostatic imbalance leading to clot formation. Congenital thrombophilia is a result of different genetic polymorphisms in the genes coding for particular elements in coagulation and fibrinolysis processes and is connected with excessive readiness to thrombosis in the carriers the mutated alleles. A higher coagulation activity has been observed in case of pregnant women who are carriers of congenital thrombophilia, when compared to the pre-pregnancy activity. These changes concern first of all utero-placental circulation, and may lead to many complications during pregnancy such as: recurrent miscarriages, intrauterine fetal death in second and third trimester, preeclampsia/eclampsia, intrauterine growth restriction and placental abruption. Numerous research indicates that anticoagulation prophylaxis in pregnant women with the abovementioned complications in medical history might prevent a similar condition in the following pregnancies. What is more, it underlines that administration of low molecular weight heparin and acetylsalicylic acid may improve perinatal outcome in thrombophilic women. However, the notion whether anticoagulant prophylaxis should be applied in women with preeclampsia, fetal hypotrophy or fetal loss remains disputable. Furthermore, the question of when the prophylaxis should start and of its duration remains unanswered. The following summary focuses on congenital thrombophilia in pregnant women with burdened anamnesis and suggested pattern of anticoagulation prophylaxis.

Recombinant factor VIIa in the management of postpartum bleeds: an audit of clinical use.

BACKGROUND: This paper presents an analysis of 25 patient cases in which recombinant factor VIIa was used in the management of postpartum hemorrhage, including severe and/or life-threatening bleeds. Anecdotal experiences in the empirical use of this agent are described and dosing regimens, effects on bleeding, and safety data are presented. METHODS: Data were extracted from the international, internet-based, voluntary registry, haemostasis.com. Search results were manually cross-checked against monthly summary reports and cases of confirmed postpartum hemorrhage were analyzed by the authors. Case providers were contacted individually to approve the use of their cases, supply any missing data, and validate the data already held. RESULTS: Of 43 reported gynecological admissions for hemorrhage, 13 were excluded as they did not relate to childbirth, and 5 due to insufficient data. The remaining 25 records, all associated with postpartum hemorrhage, were submitted by 14 doctors from 5 countries. Following administration of recombinant factor VIIa, bleeding stopped in 18 cases (72%), markedly decreased in 2 (8%), and decreased in 4 (16%). Bleeding increased following recombinant factor VIIa administration in only 1 patient (4%). Requirements for replacement blood products and crystalloids/colloids were also greatly curtailed. A full recovery was achieved by most patients (22/25, 88%) with few complications, even when recombinant factor VIIa was administered as salvage therapy. There were no thrombotic complications associated with recombinant factor VIIa administration. CONCLUSIONS: This review provides the largest aggregate of cases in which recombinant factor VIIa has been used to control obstetrical bleeding. A review of these cases suggests that this agent may be a useful and safe adjunctive therapy in the management of postpartum hemorrhage.

[Effect of recombinant activated factor VII (RFVIIA; NovoSeven) in a patient in haemorrhagic shock after obstetrical hysterectomy]. / Efekt zastosowania rekombinowanego aktywowanego czynnika VII. (RFVIIA; NovoSeven) u pacjentki we wstrzasie krwotocznym po histerektomii polozniczej.

Perinatal bleeding may lead to a fatal outcome in about 10% of cases. We present a case of a 29 year old woman in childbirth, in whom a preparation of recombinant activated factor VII (rFVIIa, NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) was used with success to control intraoperative bleeding during haemorrhagic shock after caesarean section and obstetrical hysterectomy, in the course of the patient's third abdominal cavity revision for continuing blood loss. Administration of the preparation enabled for quick intraoperative control of haemorrhage, which allowed safe and clear identification and elimination of the cause of bleeding. No significant clotting abnormalities were noted at postoperative monitoring of the coagulation system. rFVIIa seems to be an effective alternative treatment of life-threatening haemorrhages in obstetrics, allowing for quick arrest of bleeding, and thus safe control of intraoperative local hemostasis.