How to Manage Venous Thromboembolism Risk during Pregnancy in Patients with Inherited Antithrombin Deficiency?

Inherited antithrombin deficiency (ATD) is associated with a high risk of venous thromboembolic complications. Association of ATD with other conditions such as pregnancy obviously increases thromboembolic risk and may require anticoagulant therapy for prevention. Although there are several/heterogenous international guidelines regarding thromboprophylaxis in pregnant patients with ATD, data on anticoagulant prophylaxis in this context are scarce in the literature.

Procoagulant Platelet Characterization by Measuring Phosphatidylserine Exposure and Microvesicle Release from Human Purified Platelets.

Activated platelets promote coagulation primarily by exposing the procoagulant phospholipid phosphatidylserine (PS) on their outer membrane surfaces and releasing PS-expressing microvesicles that retain the original membrane architecture and cytoplasmic components of their originating cells. The accessibility of phosphatidylserine facilitates the binding of major coagulation factors, significantly amplifying the catalytic efficiency of coagulation enzymes, while microvesicle release acts as a pivotal mediator of intercellular signaling. Procoagulant platelets play a crucial role in clot stabilization during hemostasis, and their increased proportion in the bloodstream correlates with an increased risk of thrombosis.

Efficacy and safety of recombinant activated factor VII in Glanzmann thrombasthenia: A systematic literature review.

Background: Platelet transfusion is considered the standard treatment for preventing or controlling severe haemorrhage in Glanzmann thrombasthenia (GT). However, platelet transfusion can have detrimental effects, including the production of anti-GPIIb/IIIa isoantibodies or anti-HLA antibodies (Ab) and platelet transfusion refractoriness. Recombinant activated factor VII (rFVIIa) has been proposed as an alternative treatment to platelet transfusion.

Targeting tissue factor pathway inhibitor with concizumab to improve hemostasis in patients with Glanzmann thrombasthenia: an in vitro study.

Background: Glanzmann thrombasthenia (GT) is caused by an inherited defect of platelet αβ integrin. Concizumab, a monoclonal antibody specific for tissue factor pathway inhibitor, abolishes its anticoagulant effect.

Objectives: To evaluate the in vitro ability of concizumab to improve hemostasis in GT.

Association of laboratory test results with the bleeding history in patients with inherited platelet function disorders (the Bleeding Assesment Tool - LABoratory tests substudy): communication from the Platelet Physiology ISTH-SSC.

Background: In hemophilia and von Willebrand disease, the degree of alteration of laboratory assays correlates with bleeding manifestations. Few studies have assessed the predictive value for bleeding of laboratory assays in patients with inherited platelet function disorders (IPFDs).

Objectives: To assess whether there is an association between platelet function assay results and bleeding history, as evaluated by the International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool (BAT).

characterization of rare anti-αβ isoantibodies produced by patients with Glanzmann thrombasthenia that severely block fibrinogen binding and generate procoagulant platelets via complement activation.

Background: Glanzmann thrombasthenia (GT) is a rare bleeding disorder caused by inherited defects of the platelet αβ integrin. Platelet transfusions can be followed by an immune response that can block integrin function by interfering with fibrinogen binding.

Objectives: In this study, we aimed to determine the prevalence of such isoantibodies and better characterize their pathogenic properties.

Emergency management of patients with Glanzmann thrombasthenia: consensus recommendations from the French reference center for inherited platelet disorders.

Glanzmann thrombasthenia (GT) is a genetic bleeding disorder characterised by severely reduced/absent platelet aggregation in response to multiple physiological agonists. The severity of bleeding in GT varies markedly, as does the emergency situations and complications encountered in patients. A number of emergency situations may occur in the context of GT, including spontaneous or provoked bleeding, such as surgery or childbirth.

Multicenter evaluation of light transmission platelet aggregation reagents: communication from the ISTH SSC Subcommittee on Platelet Physiology.

Background: Light transmission aggregation (LTA) is used widely by the clinical and research communities. Although it is a gold standard, there is a lack of interlaboratory harmonization.

Objectives: The primary objective was to assess whether sources of activators (mainly adenosine diphosphate [ADP], collagen, arachidonic acid, epinephrine, and thrombin receptor activating peptide6) and ristocetin contribute to poor LTA reproducibility.

Combined Platelet and Red Blood Cell Recovery during On-pump Cardiac Surgery Using same™ by i-SEP Autotransfusion Device: A First-in-human Noncomparative Study (i-TRANSEP Study).

Background: Centrifugation-based autotransfusion devices only salvage red blood cells while platelets are removed. The same™ device (Smart Autotransfusion for ME; i-SEP, France) is an innovative filtration-based autotransfusion device able to salvage both red blood cells and platelets. The authors tested the hypothesis that this new device could allow a red blood cell recovery exceeding 80% with a posttreatment hematocrit exceeding 40%, and would remove more than 90% of heparin and 75% of free hemoglobin.

Obstetrical complications in hereditary fibrinogen disorders: the Fibrinogest study.

Background: Women with hereditary fibrinogen disorders (HFDs) seem to be at an increased risk of adverse obstetrical outcomes, but epidemiologic data are limited.

Objectives: We aimed to determine the prevalence of pregnancy complications; the modalities and management of delivery; and the postpartum events in women with hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia.

Methods: We conducted a retrospective and prospective multicentric international study.

Platelet function studies in myeloproliferative neoplasms patients with or mutation.

Background: and mutations are the most frequent molecular causes of -negative myeloproliferative neoplasms (MPN). Patients with mutations are at lower risk of thrombosis than patients with . We hypothesized that -mutated blood platelets would have platelet function defects that might explain why these patients are at lower risk of thrombosis.

High Rates of Anti-αIIbβ3 Antibodies Produced by a Glanzmann Thrombasthenia Patient after First and Unique Red Blood Cells Administration.

Immunization against the platelet αIIbβ3 glycoprotein due to blood transfusion represents one of the most severe complications in Glanzmann thrombasthenia (GT) disease. Anti-αIIbβ3 isoantibodies development may lead to ineffective platelet transfusion and can, in case of pregnancy, cross the placenta leading to fetal thrombocytopenia. We describe here the case of a girl with type I GT who developed high rates of anti-αIIbβ3 isoantibodies after first and unique blood transfusion.

How I manage pregnancy in women with Glanzmann thrombasthenia.

Glanzmann thrombasthenia (GT) is a rare inherited platelet function disorder caused by a quantitative and/or qualitative defect of the αIIbβ3 integrin. Pregnancy and delivery are recognized risk periods for bleeding in women with GT. The newborn may also be affected by fetal and neonatal immune thrombocytopenia induced by the transplacental passage of maternal anti-αIIbβ3 antibodies, which can lead to severe hemorrhage and fetal loss.

Comparison of different activators of coagulation by turbidity analysis of hereditary dysfibrinogenemia and controls.

Turbidity analysis is widely used as a quantitative technique in hereditary dysfibrinogenemia. We aimed to compare several coagulation triggers in hereditary dysfibrinogenemia and control plasmas. We included 20 patients with hereditary dysfibrinogenemia, 19 with hotspot mutations Aα Arg35His (n = 9), Aα Arg35Cys (n = 2), γ Arg301His (n = 6), γ Arg301Cys (n = 2), and one with Aα Phe27Tyr, and a commercial pooled normal plasma.

Immunization against α β and α β in Glanzmann thrombasthenia patients carrying the French Gypsy mutation.

Essentials The c.1544+1G>A mutation was identified in Gypsy Glanzmann thrombasthenia (GT) patients. Gypsy GT patients express normal α β carrying HPA-1b epitopes.

BLOC1S5 pathogenic variants cause a new type of Hermansky-Pudlak syndrome.

Purpose: Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, excessive bleeding, and often additional symptoms. Variants in ten different genes have been involved in HPS. However, some patients lack variants in these genes.

A new case with Hermansky-Pudlak syndrome type 9, a rare cause of syndromic albinism with severe defect of platelets dense bodies.

Hermansky-Pudlak syndrome (HPS) is a rare form of syndromic oculocutaneous albinism caused by disorders in lysosome-related organelles. Ten genes are associated with different forms of HPS. HPS type 9 (HPS-9) is caused by biallelic variants of .