RESUMO
Coagulation factor inhibitors (CFIs) sometimes cause fatal bleeding conditions. Determination of an inhibitor titer (INH-titer) using the Bethesda method is essential for diagnosing diseases associated with CFIs and examining the effects of immunosuppressive therapy. We reviewed 17 cases with CFIs (acquired hemophilia A, n = 11; FV inhibitor, n = 6) to examine the usefulness of determining quantities of an autoantibody to a coagulation factor (CF-IgG) by ELISA for diagnosis and therapeutic efficacy, as compared with INH-titer. One patient with an INH-titer and no evidence of CF-IgG was lupus anticoagulant (LA)-positive, and thus the positive INH-titer may have been a false positive caused by LA. Although INH-titer alone was insufficient to correctly identify patients with CFI, determination of CF-IgG appeared to be useful. In addition, even after INH-titer disappearance, hemorrhagic conditions recurred when CF-IgG was detected. These findings suggest that the presence of a clearance antibody against the coagulation factor might reduce the activity of that coagulation factor even after disappearance of the corresponding neutralizing antibody. Although the diagnosis and therapeutic efficacy can also be determined by INH-titer disappearance and improvement of corresponding coagulation factor activity, determination of CF-IgG by ELISA can improve the accuracy of these assessments.
Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico , Fator VIII/imunologia , Fator V/imunologia , Hemofilia A/diagnóstico , Imunoglobulina G/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-IdadeRESUMO
Factor V inhibitors are a rare cause of life-threatening bleeding. We present a case of an acquired factor V inhibitor likely caused by coronavirus disease 2019 infection. Bleeding was manifested by severe anemia requiring frequent red-cell transfusion, left psoas muscle hematoma, and left retroperitoneal cavity hematoma. Factor V activity was less than 1% and the factor V inhibitor titer was 31.6 Bethesda units. Severe acute respiratory syndrome coronavirus 2 RNA testing of the nasopharynx was positive 2 weeks before presentation and continued to be positive for 30 days. The patient failed treatment with intravenous immunoglobulin and dexamethasone. Three cycles of plasmapheresis with fresh frozen plasma replacement resulted in correction of the bleeding and laboratory coagulopathy. This is the first reported case of a factor V inhibitor in a coronavirus disease 2019 patient and suggests that plasmapheresis may be a successful treatment strategy.
Assuntos
Autoanticorpos/biossíntese , COVID-19/sangue , Fator V/imunologia , Transtornos Hemorrágicos/etiologia , SARS-CoV-2 , Idoso de 80 Anos ou mais , Anemia/etiologia , Anemia/terapia , Anticorpos Antivirais/sangue , Especificidade de Anticorpos , Autoanticorpos/imunologia , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/imunologia , Terapia Combinada , Comorbidade , Diagnóstico Tardio , Dexametasona/uso terapêutico , Transfusão de Eritrócitos , Fator V/antagonistas & inibidores , Feminino , Hematoma/etiologia , Transtornos Hemorrágicos/tratamento farmacológico , Transtornos Hemorrágicos/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Inibidor de Coagulação do Lúpus/sangue , Octreotida/uso terapêutico , Plasma , Plasmaferese , SARS-CoV-2/imunologia , Vitamina K/uso terapêuticoRESUMO
Acquired factor V inhibitor (AFVI) is an extremely rare disorder that may cause severe bleeding. To identify factors associated with bleeding risk in AFVI patients, a national, multicentre, retrospective study was made including all AFVI patients followed in 21 centres in France between 1988 and 2015. All patients had an isolated factor V (FV) deficiency <50% associated with inhibitor activity. Patients with constitutional FV deficiency and other causes of acquired coagulation FV deficiencies were excluded. The primary outcome was incident bleeding and factors associated with the primary outcome were identified. Thirty-eight (74 [36-100] years, 42·1% females) patients with AFVI were analysed. Bleeding was reported in 18 (47·4%) patients at diagnosis and in three (7·9%) during follow-up (7 [0·2-48.7] months). At diagnosis, FV was <10% in 31 (81·6%) patients. Bleeding at diagnosis was associated with a prolonged prothrombin time that strongly correlated with the AFVI level measured in plasma {r = 0·63, 95% confidence interval (CI) [0·36-0·80], P < 0·05}. Bleeding onset during follow-up was associated with a slow AFVI clearance (P < 0·001). The corresponding receiver operating characteristics curve showed that AFVI clearance was predictive of bleeding onset with an AFVI clearance of seven months with a sensitivity of 100% (95% CI: 29-100) and a specificity of 86% (95% CI: 57-98, P = 0·02). Kaplan-Meier analysis showed that AFVI clearance >7 months increased the risk of bleeding by 8 (95% CI: [0·67-97], P = 0·075). Prothrombin time at diagnosis and time for clearance of FV inhibitor during follow-up are both associated with bleeding in patients with AFVI.
Assuntos
Fator V/antagonistas & inibidores , Hemorragia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Autoanticorpos/imunologia , Comorbidade , Reações Cruzadas , Fator V/imunologia , Feminino , Seguimentos , França/epidemiologia , Hemorragia/epidemiologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulinas Intravenosas/efeitos adversos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Isoanticorpos/imunologia , Masculino , Pessoa de Meia-Idade , Tempo de Protrombina , Estudos Retrospectivos , RiscoRESUMO
Factor V deficiency is a rare hemostatic disorder. It may present with a diverse spectrum of symptoms due to a variety of mechanisms including development of autoantibodies associated with a number of conditions. We report a first case of factor V deficiency in Tunisian hemodialysis patient due to an autoantibody most likely secondary to antibiotic exposure responsible for an arteriovenous shunt thrombosis rather than bleeding. We discuss here the clinical and biological features of acquired factor V inhibitor and provide a short review of the current literature.
Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Autoanticorpos/sangue , Transtornos da Coagulação Sanguínea/etiologia , Fator V/imunologia , Diálise Renal , Trombose/etiologia , Idoso , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Fator V/antagonistas & inibidores , Humanos , Masculino , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Trombose/sangue , Trombose/diagnóstico , TunísiaAssuntos
Coagulação Sanguínea/imunologia , Fator V/imunologia , Ativação Plaquetária/imunologia , Coagulação Sanguínea/efeitos dos fármacos , Feminino , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/imunologia , Hemorragia Gastrointestinal/fisiopatologia , Humanos , Pessoa de Meia-Idade , Ativação Plaquetária/efeitos dos fármacosAssuntos
Testes de Coagulação Sanguínea/métodos , Deficiência do Fator V/diagnóstico , Fator V/metabolismo , Trombina/biossíntese , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Autoanticorpos/imunologia , Fator V/genética , Fator V/imunologia , Deficiência do Fator V/sangue , Deficiência do Fator V/genética , Humanos , MasculinoAssuntos
Antibacterianos/efeitos adversos , Autoanticorpos/imunologia , Doenças Autoimunes/terapia , Ceftriaxona/efeitos adversos , Deficiência do Fator V/terapia , Fator V/imunologia , Transfusão de Plaquetas , Cuidados Pré-Operatórios/métodos , Substituição da Valva Aórtica Transcateter , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Anticoagulantes/uso terapêutico , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Ceftriaxona/uso terapêutico , Terapia Combinada , Emergências , Deficiência do Fator V/diagnóstico , Deficiência do Fator V/imunologia , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Tempo de Tromboplastina Parcial , Prednisona/uso terapêutico , Tempo de Protrombina , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Infecções Urinárias/complicações , Infecções Urinárias/tratamento farmacológicoAssuntos
Antibacterianos/efeitos adversos , Antifúngicos/efeitos adversos , Autoanticorpos/imunologia , Doenças Autoimunes/induzido quimicamente , Deficiência do Fator V/induzido quimicamente , Fator V/imunologia , Pneumonia/tratamento farmacológico , Idoso , Antibacterianos/administração & dosagem , Especificidade de Anticorpos , Antifúngicos/administração & dosagem , Ceftriaxona/efeitos adversos , Cefalosporinas/efeitos adversos , Ciprofloxacina/efeitos adversos , Substituição de Medicamentos , Quimioterapia Combinada , Fluoroquinolonas/efeitos adversos , Humanos , Levofloxacino/efeitos adversos , Masculino , Meropeném/efeitos adversos , Micafungina/efeitos adversos , Tempo de Tromboplastina Parcial , Tempo de ProtrombinaRESUMO
An 87-year-old man with diabetes mellitus was admitted to control recurrent bleeding from hemodialysis puncture sites. He was a smoker and had been diagnosed with arteriosclerosis obliterans. His PT and APTT were markedly prolonged, and all coagulation factors were markedly decreased (factor V [FV] activity < 1%) or below the measurement threshold, with the exception of fibrinogen and factor XIII. Neither PT nor APTT were corrected upon mixing with normal plasma. A high titer of FV inhibitor was found at 415 BU/mL, and anti-FV autoantibody was detected by both immunoblot assay and ELISA. Prednisolone administration and plasma exchange partially improved prolonged PT and APTT and decreased the FV inhibitor level. Five months later, he manifested symptoms of severe ischemia in both legs. Angiography revealed diffuse stenosis downstream of both common iliac arteries. Endovascular therapy was repeated four times, the prednisolone dose was reduced, and low-dose antiplatelet therapy was initiated. After the final successful endovascular therapy, arterial thrombosis was detected using ultrasound and angiography. Aspiration thrombectomy and thrombolytic therapy failed to achieve recanalization, and necrosis of the legs worsened. Despite the severe coagulation abnormalities, vascular interventions should have been performed with regular-dose antiplatelet therapy, as the patient exhibited multiple risk factors for atherothrombosis.
Assuntos
Autoanticorpos/sangue , Fator V/imunologia , Idoso de 80 Anos ou mais , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Testes de Coagulação Sanguínea , Hemorragia/sangue , Humanos , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , Prednisolona , Diálise Renal/efeitos adversos , Trombose/diagnóstico por imagem , Resultado do TratamentoRESUMO
BACKGROUND: Coagulation factor V inhibitors (FV-i) may occur in patients with congenital FV deficiency or previously hemostatically normal patients (autoimmune (AI)-FV-i). Most of the published literature is confined to case reports. OBJECTIVE: Describe clinical and laboratory features of AI-FV-i identified through the Special Coagulation Laboratory at Mayo Clinic, Rochester, Minnesota. METHODS: In this retrospective study individuals with FV-i screens performed from January 1999 to February 2017 were identified through the special coagulation laboratory database. Clinical presentation, management, and outcomes were collected for our institutional patients while detailed laboratory data was collected for all tested patients. RESULTS: Of patients with FV-i managed at our institution, 2/8 (25%) patients experienced no bleeding. There was no correlation between inhibitor titers and/or FV activity (FV:C) levels and clinical bleeding. Hemostatic management included fresh frozen plasma, platelet transfusion, activated prothrombin complex concentrates, and recombinant factor VIIa. Only 2 patients received immunomodulatory treatment. FV-i mixing studies with normal pooled plasma (nâ¯=â¯26) demonstrated inhibition on immediate mix but progressive inhibition after 1â¯h of incubation could not be demonstrated. 71% of platelet neutralization procedures were falsely positive while 59% of DRVVT assays were indeterminate. CONCLUSION: FV-i demonstrates immediate inhibition on mixing studies; however our limited data does not support a time dependent inhibition. Our clinical cohort confirms the variable clinical phenotype for individuals with FV-i and supports the notion that management of FV-i should be guided by clinical symptoms and not FV:C or FV-i titer.
Assuntos
Autoimunidade , Inibidores dos Fatores de Coagulação Sanguínea/imunologia , Deficiência do Fator V/complicações , Fator V/imunologia , Hemorragia/etiologia , Hemorragia/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Transfusão de Sangue , Fator V/análise , Deficiência do Fator V/sangue , Deficiência do Fator V/congênito , Deficiência do Fator V/imunologia , Feminino , Hemorragia/sangue , Hemorragia/imunologia , Hemostáticos/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoAssuntos
Inibidores dos Fatores de Coagulação Sanguínea/imunologia , Fator V/imunologia , Fator Xa/imunologia , Adesivo Tecidual de Fibrina/efeitos adversos , Hemorragia/etiologia , Imunoglobulina G/imunologia , Idoso , Animais , Coagulação Sanguínea , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Bovinos , Feminino , Adesivo Tecidual de Fibrina/imunologia , Hemorragia/sangue , Hemorragia/imunologia , Hemorragia/terapia , Humanos , Imunoglobulina G/sangueAssuntos
Anemia Refratária com Excesso de Blastos/complicações , Doenças Autoimunes/etiologia , Azacitidina/uso terapêutico , Deficiência do Fator V/etiologia , Fator V/imunologia , Idoso de 80 Anos ou mais , Anemia Refratária com Excesso de Blastos/tratamento farmacológico , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Azacitidina/efeitos adversos , Diagnóstico Precoce , Deficiência do Fator V/tratamento farmacológico , Deficiência do Fator V/imunologia , Hemorragia Gengival/etiologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Tempo de Tromboplastina Parcial , Prednisona/uso terapêutico , Tempo de ProtrombinaRESUMO
Historically, inhibitors to coagulation factor V (FV) most often have developed in patients treated with bovine thrombin, a topical hemostatic agent used during surgical procedures. With the advent of newer hemostatic agents, and the concurrent diminished use of bovine thrombin, the incidence of FV inhibitors has fallen. Nevertheless, FV inhibitors are occasionally seen on an idiopathic basis as well as in association with medications, malignancies, autoimmune disorders, pregnancy, and infections. Factor V inhibitors may present with life-threatening bleeding or thrombosis, or they may be discovered incidentally as a coagulation screening test abnormality. Management of patients with FV inhibitors is challenging and consists of control of bleeding and eradication of the inhibitor. In this short overview we review the role of platelet and plasma FV in hemostasis and discuss the unique characteristics, clinical features, diagnosis, treatment, and prognosis associated with FV inhibitors.
Assuntos
Fator V/antagonistas & inibidores , Animais , Autoanticorpos/sangue , Bovinos , Diagnóstico Diferencial , Fator V/imunologia , Feminino , Hemorragia/etiologia , Hemostáticos/efeitos adversos , Humanos , Gravidez , Trombina/efeitos adversosRESUMO
INTRODUCTION: The thrombomodulin (TM)/activated protein C (APC) system is a key regulator of haemostasis, limiting amplification and propagation of the formed blood clot to the injury site. Dampening APC's inhibition of factor V (FV) and factor VIII (FVIII) may be a future strategy in developing next-generation therapeutic targets for haemophilia treatment. AIMS: To determine ex vivo the respective concentration-dependent effects of TM and a FV-stabilizing Fab on the APC regulatory pathway in severe FVIII-deficient blood and plasma. METHODS: Ten severe haemophilia A subjects and one healthy control were enrolled. Blood was spiked with TM (0, 1, 2.5, 5, 10, 20.0 nmol/L) and FV-stabilizing Fab (0, 3, 15, 65, 300 nmol/L). The respective effects were compared to FVIII concentrations of 3- and 10% using rotational thromboelastometry clotting time (CT) and thrombin generation analysis (TGA). RESULTS: With 1 and 2.5 nmol/L TM, 5% FVIII resulted in CT similar to the absence of TM, suggesting it completely reversed the effect of APC. Increasing TM concentrations also reduced peak thrombin generation and ETP. The addition of 300 nmol/L FV-stabilizing Fab returned CT to nearly baseline, but for most subjects was less than the effects of 3- or 10% FVIII. The FV-stabilizing Fab produced similar or greater thrombin generation compared to samples with 3- or 10% FVIII. CONCLUSIONS: The FV-stabilizing Fab resulted in enhanced CT and TGA parameters consistent with FVIII levels of 3- and 10%. Additional studies need to further characterize how modulating the APC pathway may prove beneficial in developing new haemophilia drug targets.
Assuntos
Hemofilia A/sangue , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Proteína C/metabolismo , Trombomodulina/administração & dosagem , Fator V/imunologia , Fator V/metabolismo , Fator VIII/administração & dosagem , Fator VIII/metabolismo , Hemofilia A/tratamento farmacológico , Hemofilia A/patologia , Hemostasia/efeitos dos fármacos , Humanos , Fragmentos Fab das Imunoglobulinas/imunologia , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Tromboelastografia , Trombina/metabolismoRESUMO
Stem cell-derived platelets have the potential to replace donor platelets for transfusion. Defining the platelet-producing megakaryocytes (MKs) within the heterogeneous MK culture may help to optimize the in vitro generation of platelets. Using 2 human stem cell models of megakaryopoiesis, we identified novel MK populations corresponding to distinct maturation stages. An immature, low granular (LG) MK pool (defined by side scatter on flow cytometry) gives rise to a mature high granular (HG) pool, which then becomes damaged by apoptosis and glycoprotein Ib α chain (CD42b) shedding. We define an undamaged HG/CD42b+ MK subpopulation, which endocytoses fluorescently labeled coagulation factor V (FV) from the media into α-granules and releases functional FV+CD42b+ human platelet-like particles in vitro and when infused into immunodeficient mice. Importantly, these FV+ particles have the same size distribution as infused human donor platelets and are preferentially incorporated into clots after laser injury. Using drugs to protect HG MKs from apoptosis and CD42b shedding, we also demonstrate that apoptosis precedes CD42b shedding and that apoptosis inhibition enriches the FV+ HG/CD42b+ MKs, leading to increased platelet yield in vivo, but not in vitro. These studies identify a transition between distinct MK populations in vitro, including one that is primed for platelet release. Technologies to optimize and select these platelet-ready MKs may be important to efficiently generate functional platelets from in vitro-grown MKs.
Assuntos
Plaquetas/citologia , Células da Medula Óssea/imunologia , Fator V/genética , Células Progenitoras de Megacariócitos/citologia , Megacariócitos/citologia , Animais , Apoptose/efeitos dos fármacos , Arteríolas/efeitos dos fármacos , Arteríolas/imunologia , Arteríolas/lesões , Biomarcadores/sangue , Plaquetas/imunologia , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular , Linhagem da Célula/imunologia , Endocitose , Fator V/imunologia , Fator V/farmacologia , Citometria de Fluxo , Expressão Gênica , Humanos , Imunofenotipagem , Lasers , Células Progenitoras de Megacariócitos/imunologia , Megacariócitos/imunologia , Camundongos , Camundongos SCID , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Complexo Glicoproteico GPIb-IX de Plaquetas/imunologiaRESUMO
: Acquired factor V deficiency (AFVD) is a rare haemostatic disorder that is primarily because of the development of factor V inhibitors. Approximately, 200 cases have been reported and the greatest portion of these cases was because of bovine thrombin exposure. We report a case of a man who presented with haematuria followed by multiple haemorrhages associated with an elevated prothrombin time and an activated partial thromboplastin time. A workup revealed reduced factor V activity and a factor V inhibitor level of 1.9âBU, which were likely secondary to a urinary tract infection. Using corticosteroids, we successfully eliminated the inhibitor and controlled the bleeding. We review the published literature to identify the conditions that are associated with nonbovine thrombin AFVD. We assume that AFVD should be kept in mind for patients who present with multiple haemorrhages.
Assuntos
Deficiência do Fator V/diagnóstico , Fator V/imunologia , Hematúria , Hemorragia , Infecções Urinárias/patologia , Corticosteroides/uso terapêutico , Animais , Autoanticorpos/sangue , Testes de Coagulação Sanguínea , Bovinos , Diagnóstico Diferencial , Fator V/antagonistas & inibidores , Deficiência do Fator V/tratamento farmacológico , Deficiência do Fator V/etiologia , Hemorragia/tratamento farmacológico , Transtornos Hemorrágicos , Humanos , Masculino , Pessoa de Meia-Idade , Trombina , Infecções Urinárias/complicaçõesRESUMO
Acquired factor V (FV) inhibitors occur rarely and classically develop after exposure to bovine thrombin. The clinical presentation is variable, ranging from asymptomatic with incidental laboratory abnormalities to significant bleeding. With the development of human-derived thrombin agents, bovine thrombin is less frequently used. We report a case of an acquired FV inhibitor that developed in a patient after exposure to human thrombin used as a hemostatic agent during an otorhinolaryngology surgical procedure. Our review of the literature revealed only one prior reported case of FV inhibitor after exposure to human thrombin. Hematologists and surgeons should be aware of this rare, but potentially life-threatening, complication in the postprocedural setting.
Assuntos
Autoanticorpos/sangue , Perda Sanguínea Cirúrgica/prevenção & controle , Deficiência do Fator V/induzido quimicamente , Fator V/imunologia , Hemostáticos/efeitos adversos , Procedimentos Cirúrgicos Otorrinolaringológicos , Hemorragia Pós-Operatória/prevenção & controle , Trombina/efeitos adversos , Administração Tópica , Idoso , Biomarcadores/sangue , Fator V/metabolismo , Deficiência do Fator V/sangue , Deficiência do Fator V/diagnóstico , Deficiência do Fator V/imunologia , Feminino , Hemostáticos/administração & dosagem , Humanos , Procedimentos Cirúrgicos Otorrinolaringológicos/efeitos adversos , Trombina/administração & dosagem , Fatores de TempoRESUMO
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.