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Acquired von Willebrand syndrome (AVWS) contributes to bleeding during extracorporeal membrane oxygenation (ECMO) support. Although it is recognized that AVWS rapidly resolves after ECMO decannulation, this approach may often be clinically unsuitable. In such cases, optimal AVWS management during ECMO support is not well established. We report our approach to managing AVWS in a patient on veno-venous (VV) ECMO for 59 days. A 19-year-old male developed hypoxemic respiratory failure from SARS-CoV-2 pneumonia. Following intubation, he progressed to VV-ECMO support for refractory hypoxemia and was started on bivalirudin for systemic anticoagulation. Two days later, he developed refractory gastrointestinal and oro-nasopharyngeal bleeding despite blood product transfusions and discontinuing bivalirudin. He was started on pantoprazole along with infusions of octreotide and aminocaproic acid. Upper endoscopy on ECMO day 5 revealed an ulcerative bleeding vessel in the duodenum that was clipped. Recurrent mucosal bleeding precluded resumption of systemic anticoagulation. On ECMO day 23, AVWS was diagnosed based on elevated von Willebrand factor (VWF) activity (207%, normal 55-189%) and antigen (234%, normal 50-210%) levels with abnormally low VWF high-molecular-weight multimers. Factor VIII complex was administered twice over the following week. Between doses, the ECMO circuit was exchanged to empirically mitigate suspected shear-related VWF consumption from the fibrin burden, and a repeat endoscopy controlled additional intestinal bleeding with local hemostatic agents. He received 36 units of red blood cells, 2 units of platelets, 2 units of plasma, and 7 pooled units of cryoprecipitate over 31 days leading into these combined interventions. In the 28 days afterwards, he received 3 units of red blood cells, 3.5 pooled units of cryoprecipitate, and no additional platelets or plasma. Our patient was maintained off systemic anticoagulation for 54 of 59 days of VV-ECMO support without any thrombotic complications occurring. With no subsequent clinical evidence of bleeding, repeat VWF testing was done two months post-decannulation and showed near-normal VWF activity (54%) and normal multimer distribution. Our patient rehabilitated well without any neurologic deficits and on discharge was requiring supplemental oxygen with sleep and strenuous activity. Avoiding systemic anticoagulation, repleting VWF, maintaining circuit integrity, and providing local hemostasis, when possible, may be a safe and effective management strategy of AVWS on ECMO support when decannulation is not a viable option.
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The A and B oligosaccharide antigens of the ABO blood group system are produced from the common precursor, H substance, by enzymatic reactions catalyzed by A and B glycosyltransferases (AT and BT) encoded by functional A and B alleles at the ABO genetic locus, respectively. In 1990, my research team cloned human A, B, and O allelic cDNAs. We then demonstrated this central dogma of ABO and opened a new era of molecular genetics. We identified four amino acid substitutions between AT and BT and inactivating mutations in the O alleles, clarifying the allelic basis of ABO. We became the first to achieve successful ABO genotyping, discriminating between AA and AO genotypes and between BB and BO, which was impossible using immunohematological/serological methods. We also identified mutations in several subgroup alleles and also in the cis-AB and B(A) alleles that specify the expression of the A and B antigens by single alleles. Later, other scientists interested in the ABO system characterized many additional ABO alleles. However, the situation has changed drastically in the last decade, due to rapid advances in next-generation sequencing (NGS) technology, which has allowed the sequencing of several thousand genes and even the entire genome in individual experiments. Genome sequencing has revealed not only the exome but also transcription/translation regulatory elements. RNA sequencing determines which genes and spliced transcripts are expressed. Because more than 500,000 human genomes have been sequenced and deposited in sequence databases, bioinformaticians can retrieve and analyze this data without generating it. Now, in this era of genomics, we can harness the vast sequence information to unravel the molecular mechanisms responsible for important biological phenomena associated with the ABO polymorphism. Two examples are presented in this review: the delineation of the ABO gene evolution in a variety of species and the association of single nucleotide variant (SNV) sites in the ABO gene with diseases and biological parameters through genome-wide association studies (GWAS).Copyright © Annals of Blood. All rights reserved.
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Background: Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder that occurs in a sporadic, nonhereditary pattern. It is caused by circulating autoantibodies against clotting factor VIII that are triggered by several conditions. Moreover, AHA is clinically distinct from the inherited form of hemophilia A, with a different natural history and management approach, necessitating a high-index of suspicion in at-risk patients. Coronavirus disease 2019 (COVID-19) has emerged as a multisystemic disease whose manifestations are continuously being evaluated. There are few case reports of AHA associated with COVID-19 infection, while one case of AHA has been associated with COVID-19 vaccination. Similarly, deep venous thrombosis (DVT) frequently complicates COVID-19 infection, but two cases of DVT have been reported following COVID-19 vaccination. We report the occurrence of both AHA and DVT in a 63-year-old male patient within one week of receiving his first dose of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine. Case Description: Patient is a 63-year-old male who presented with a 3-day history of left lower extremity (LLE) swelling and pain. He was hemodynamically stable, but examination showed exquisite tenderness, ecchymosis, and pitting edema at the calf of the LLE. He had normal platelet counts at presentation but had mild anemia (11.9 g/dL) and elevated activated partial thromboplastin time (APTT) of 68.0 seconds. Venous Doppler ultrasound showed acute DVT in the left popliteal vein, necessitating commencement on heparin drip. He developed progressively worsening hematomas, symptomatic anemia that required red cell transfusions, and persistently elevated APTT despite stopping the heparin drip. Work up for pulmonary embolism, malignancy, and disseminated intravascular coagulopathy (DIC) were negative. Antiphospholipid antibodies and lupus anticoagulant were also negative. He had low factor VIII levels, tested positive for factor VIII inhibitor, and PTT mixing studies were consistent with acquired factor inhibitor. Treatment involved administration of Factor Eight Inhibitor Bypassing Activity (FEIBA) as well as intravenous methylprednisolone and cyclophosphamide. Following resolution of active bleeding with evidence of stable hemoglobin concentration, he was discharged home on oral prednisone and cyclophosphamide. Conclusion(s): This case report highlights the possibility of AHA and DVT as rare, potentially life-threatening adverse events that could occur following COVID-19 vaccination, which is currently the most effective tool employed in controlling the COVID-19 pandemic.Copyright © Annals of Blood. All rights reserved.
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Introduction Side effects may occur after vaccination against COVID-19. Temporary reactions such as redness, swelling and pain at the injection site, high temperature, fever, tiredness, etc. may be signs of the body's response to the vaccine. Such reactions usually develop within two days after vaccination and last for a few days. With the growing number of vaccinations against SARSCoV- 2 a rising number of reports also showed serious side effects. In some of the most severe cases, life-threatening thrombotic events may develop. We present a case that shows further symptoms that may be due to an immune reaction to the vaccine. Method In this case report a 67 male smoker presented to our outpatient clinic in April 2022. A few days after vaccination against SARS-CoV-2 with an mRNA vaccine the patient developed pain at all finger tips. The clinical examination showed cool and livid discoloration of all fingers to different degrees;toes were not involved. The symptoms developed progressively over the following weeks into a severe form with progressive fingertip skin necrosis. Results The blood test showed a CRP of 9.18 mg/l (reference range: 0-3 mg/l) as well as an increased fibrinogen and factor VIII activity. D-dimers were only slightly increased to 290 ng/ml (reference range: < 230 ng/ml) during initial examination. Cold agglutinins, cryoglobulin and cryofibrinogen were tested negative. Angiologic examination revealed small multiple thrombi in the ulnar and digital arteries. Furthermore, the resting ECG showed no dilated ventricles and no indication of a hemodynamically relevant defect. The assessment revealed a good cardiac function overall with no evidence of embolism. Therapy was started with Nifidipine (gold standard in Raynaud's disease), Eliquis 5 mg 1-0-1, and diclofenac following hospital admission. In the further course, the therapy regimen was changed to Ilomedin IV for 4 days once a month. After two weeks, symptoms significantly improved and the signs of necrosis at the fingers disappeared. Conclusion In summary, a circulatory perfusion disorder associated with microthrombotic events may be a possible side effect of SARS CoV-2 vaccination. A combination of Nifidipine, DOAC and pain therapy has been shown to be an effective treatment of "COVID-fingers" in this case report.
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Background: With a prevalence of 1-3 cases per million, acquired haemophilia A (AHA) is a rare autoimmune bleeding disorder caused by the presence of neutralizing antibodies against factor VIII. Even though diagnosis of this bleeding disorder is rarely established among children and adolescents, AHA may lead to severe, life-threatening hemorrhage in this age group, and therefore it requires special caution. Case report: 19 year old primigravida with confirmed SARS-CoV-2 infection was admitted to hospital due to prolonged vaginal bleeding six weeks postpartum. All gynaecological causes of uterine bleeding were excluded, Foley catheter was placed, but the bleeding still persisted. Coagulation tests revealed isolated deranged aPTT values. Further haematology evaluation demonstrated factor VIII deficiency, presence of factor VIII inhibiting factors, and the diagnosis of AHA was proposed. The anti-inhibitor coagulant complex drug was introduced and patient has responded positively to the treatment. Conclusion(s): Due to disturbance of immune system, pregnancy and postpartum period represent predilection time for AHA development. Furthermore, viral infection in pregnancy, such as COVID-19, might be considered as an additional risk factor for AHA development and several reported cases of AHA after COVID-19 infection support this hypothesis. Even though AHA is a rare disease, due to its high mortality rate of more than 20%, it should be considered in all cases of unusual bleeding of unknown cause in all age groups. Publication of this case report is approved by Institutional Review Board.Copyright © 2023
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Acquired hemophilia (AH) is a potentially life-threatening hemorrhagic disorder. We report the second confirmed case of COVID-19-associated AH in a 45-year-old female which, unfortunately, expired as her treatment failed. She presented to the emergency department with abnormal bleeding and spontaneous hemoptysis about ten days after a removal surgery of her epiglottis tumor. Aggregation tests, such as partial thromboplastin time (PTT), are recommended in patients with COVID-19 infection that have bleeding episodes.Copyright © 2022 The Author(s);Published by Society of Diabetic Nephropathy Prevention.
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Introduction: Acquired haemophilia A (AHA), characterized by neutralizing autoantibodies against factor VIII (FVIII), is a rare disorder (1.5/million/y). Pregnancy-relatedAHAis an even rarer disorder affecting 0.03/million/y with an incidence of 1 case/350000 births. Aim(s): to describe two pregnancy-related AHA presented at the same year of 2022. Method(s): We evaluate data from two women (patient 1 and 2) with AHA diagnosed within 1 year following childbirth. Result(s): Two women, patient 1 (P1) and P2 with 32 and 33-year old respectively, presented AHA seven (P1) and six (P2) months after delivery. They had no relevant medical history, except for COVID-19 vaccination fifteen days before the development of bleeding in P1, and late-pregnancy COVID-19 infection in P2. They had no complications related to childbirth. The bleeding events in both patients were haematuria and apparently spontaneous hematomas in the upper limb, requiring no haemostatic treatment. Laboratorial investigation, demonstrated in P1 a FVIII activity of 0.026 IU/ml and a FVIII antibody titer of 26 Bethesda Units (BU), and in P2 a FVIII activity of 0.005 IU/ml and a FVIII antibody titer of 34 BU. Concomitant disorders were excluded. The patients started eradication of the inhibitors with prednisone (1mg/kg/day orally). In P1, inhibitor titer was 0 BU and FVIII> 0.5 IU/ml after 8 weeks of immunosuppression. During eradication period, the P2 had a hematoma in right thigh treated with bypassing agent (FEIBA), but the inhibitor titer was 0 BU and FVIII>0.5 IU/ml after 1 month of inhibitor eradication. Curiously, P2 with FVIII< 0.01 IU/ml and a higher inhibitor titer than P1 had a faster response to prednisolone therapy (4 vs. 8 weeks). Currently, prednisone has been completely withdrawn in P1 and the prednisone dosage is being gradually reduced in P2. Discussion/Conclusion: Data from these two women with pregnancyrelated AHA are similar to previously described cases and expand the knowledge about this rare disorder. The peculiarity of this report is due to the emergence of two cases of a disease with markedly low incidence, in the same local and year, raising the question of whether there were new acquired factors (as immunological triggers such as COVID-19 infection or vaccination) that could be involved in the modification of the natural history of the disease. It cannot be excluded the possibility that these two cases were a coincidence.
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Introduction COVID-19 is a systemic disease associated with a high incidence of thrombotic complications. In this study we aimed to identify coagulation parameters as predictors of mortality in hospitalized patients with severe COVID- 19 infection. Method We conducted a non-interventional, national, monocentric observational study of patients treated for COVID infection at the ICU at Frankfurt University Hospital. A total of 410 patients were enrolled in the study between April 1, 2020 and December 31, 2021. Patients had to be 18 years or older and the diagnosis was confirmed by COVID real-time PCR. Coagulation parameters were analysed once on admission to the clinic and 5 to 8 days later. Variables studied included thromboplastin time, aPTT, fibrinogen, D-dimers, antithrombin, hs-troponin, all coagulation factors and vWF antigen, protein C and protein S. Data was also collected on age, sex, comorbidities, medication, and invasive ventilation, ECMO therapy and dialysis. In order to compare patients regarding their general disease status, the SAPS-II and the Horovitz index were determined at the beginning and end of the observation period. Univariate and multivariate logistic regression models were then used to screen coagulation parameters for association with mortality in critically ill COVID patients. Results The arithmetic mean age of patients was 60.9 ( +/- 14.7) years, with 76.1 % being male. Of 410 patients, 259 (63.2 %) received invasive ventilation, 95 (23.2 %) received ECMO therapy and 105 (25.6 %) received renal replacement therapy. The median inpatient length of stay was 16 (IQR: 10-29) days and ICU length of stay was 12 (IQR: 6-25) days. 176 patients (43 %) died because of their COVID disease, 234 (57 %) were discharged home or to other facilities for further treatment. In univariate logistic regression, increased age (OR = 1,029, 95 %-CI [1,013- 1,1,044]), higher SAPS-II (OR = 1,031, 95 %-CI [1,018-1,045]), fibrinogen (OR = 1,002, 95 %-CI [1,001-1,003]), FVIII (OR = 1,004, 95 %-CI [1,001-1,007]) and vWF antigen (OR = 1,005, 95 %-CI [1,003-1,007]) as well as lower antithrombin (OR = 0,981, 95 %-CI [0,971-0,991]), FII (OR = 0,983, 95 %-CI [0,972-0,993]), FXIII (OR = 0,992, 95 %-CI [0,986-0,999]), Horovitz index at admission (OR = 0,994, 95 %-CI [0,990-0,997]) and decreased protein C activity (OR = 0,989, 95 %-CI [0,982-0,996]) were associated with increased mortality. In the final multivariate regression analysis with backward elimination, low antithrombin activity (OR = 0.987, 95 %-CI [0.974-1.000]), high vWF antigen levels (OR = 1.004, 95 %-CI [1.002-1.007]) and a low Horovitz index (OR = 0.993, 95 %-CI [0.989-0.997]) were identified as independent predictive factors for increased mortality. Conclusion In the study of 410 COVID patients requiring intensive care, the Horovitz index, antithrombin activity and vWF antigen on hospital admission were identified as independent predictors of mortality.
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Introduction: Acquired hemophilia A (AHA) is a rare autoimmune disease due to anti-factor VIII antibodies. It may be associated with infections and malignancies. The association with Covid vaccine is extremely rare. Immunosuppressive therapy with steroids, cytotoxic agents, is the traditionalmainstay for antibodies eradication. Rituximab standard doses have been used with success. There are few reports on low-dose Rituximab for AHA.We present a case of AHA post Covid-19 vaccination successfully treated with low dose of Rituximab. Method(s): case report Results: A non hemophilic 69-year-old male with no medical history consulted for multiple ecchymosis that spontaneously occurred with no context of trauma. Two months previously he received a second dose of CoronaVac-Sinovac vaccine. Coagulation tests revealed an isolated and prolonged aPTT (100 sec/30s;ratio=3.33) not corrected with normal plasma. The coagulation factors assay revealed an isolated decrease of factor VIII to 1% with a titer of 121 Bethesda units/ml confirming the diagnosis of AHA. Hepatitis B and C and HIV tests were negative. A full body-computed tomography scan was normal. Treatment with Prednisolone 1 mg/kg/d was started with tranexamic acid. Bypassing therapy was not considered because of the absence of life-threatening bleeding. Seventeen days after corticosteroid initiation, a worsening of the ecchymosis was noted with the non-improvement of the aPTT. A low-dose rituximab (100 mg/week) was added for 4 weeks. After 3 doses of Rituximab a complete clinical response was achieved. Factor VIII inhibitor was completely eradicated. Corticosteroid was discontinued. At 3-month follow-up the patient remains in remission without further treatment Discussion/Conclusion:More than 50 cases of AHA following COVID-19 vaccine have been reported. To our knowledge only 2 cases of AHA were successfully treated with low dose of rituximab. Low-dose Rituximab appears to be effective for Factor VIII inhibitor eradication in AHA with a lower cost.
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Introduction: Patients with congenital bleeding disorders (CBD) have an increased bleeding tendency, which varies according to the factor deficiency and severity. In most cases, prolonged bleeding is observed after trauma, surgery and/or invasive procedures. Haemostatic treatment is needed to prevent bleeding complications and allow a good clinical outcome. Our aim is to evaluate the management of patients with CBD in minor procedures. Method(s): Retrospective study of patients with CBD who performed minor procedures over a 7-year period, through review of clinical files. Result(s): Between January 2015 and December 2021, 249 minor procedures were performed in 113 patients with CBD: 42 had diagnosis of Haemophilia A (HA) (15 severe without inhibitors;3 severe with inhibitors;4 moderate and 20 mild);12 had Haemophilia B (HB) (7 severe without inhibitors;2 moderate and 3 mild);5 were carriers of HA and 2 of HB. 35 had von Willebrand disease (VWD);15 had rare bleeding disorders (8 FVII deficiency;6 FXI deficiency;1 FX deficiency) and 2 had diagnosis of inherited platelet glycoprotein deficiencies (1 Glanzmann thrombasthenia and 1 Bernard Soulier syndrome). Most procedures were dental treatments (189);synoviorthesis/ infiltration/mesotherapy (17);endoscopies and colonoscopies (15);skin lesions excision (8);COVID-19 vaccination (5);sebaceous cyst excision (4);cardiac catheterization (3);ureteral stent removal (3);bone marrow biopsy (2);cystoscopy (2) and breast fibroadenoma excision (1). Prophylactic treatment was performed in 237 (95%) of the procedures, respectively FVIII concentrate factor (59);FIX concentrate factor (27);DDAVP (66);von Willebrand factor/factor VIII concentrates (44);bypassing agents (24);platelet (6);inactivated human plasma (9);tranexamic acid (47) and epsilon-aminocaproic acid (161). No side effects were reported. Discussion/Conclusion: Most patients that underwent minor procedures had Haemophilia and VDW(83%). The most common procedure was dental treatment (76%). Patients with CBD require attention and special care in dental practice. The haemostatic prophylactic treatment varies according to the specific haemostatic defect, severity and type of procedure. The treatment performed has been demonstrated safe and effective, with low incidences of haemorrhagic and treatment-related complications. These patients' treatment requires multidisciplinary teams and reference centres.
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Background Patients with hypoplastic left heart syndrome (HLHS) undergo a Fontan procedure as part of single ventricle surgical palliation. Post-Fontan, sluggish blood flow and an imbalance in coagulant factor proteins may predispose to thrombus formation. Other risk factors may include chylothorax as well as acute and chronic inflammation. Currently, there is no standardized surveillance strategy to detect thrombus in Fontan patients. Case A 34-month old male with HLHS underwent an extracardiac non-fenestrated Fontan complicated by chylothorax treated with 5 days of IV steroids and diuretics. He was on therapeutic aspirin. After progressive worsening of right pleural effusion, a chest tube was placed three weeks post-Fontan with continued chylous output. Stool alpha 1 antitrypsin was negative. Decision-making Given persistent chylothorax, a repeat echocardiogram was performed revealing a large mass in the Fontan circuit less than one month post-op. Cardiac CT showed occlusive thrombus filling the entirety of the Fontan conduit extending into hepatic veins and bilateral pulmonary arteries. He underwent extensive surgical thrombectomy and Fontan conduit revision. Hypercoagulable work-up revealed elevated factor 8 and von Willebrand factor activity which persisted more than one month post-op. Patient's history was also significant for COVID-19 infection 6 months prior. He was initially anticoagulated with bivalirudin with tirofiban initiated for antiplatelet therapy. He was ultimately transitioned to rivaroxaban, pentoxifylline and aspirin with chylothorax resolution over one month without thrombus recurrence. Conclusion Development of risk stratification tools to identify patients at higher risk for thrombi formation post-Fontan may facilitate patient selection for more aggressive anticoagulation. Consideration of elevated factor 8 as well as persistent or recurrent chylothorax may be beneficial, as increased thrombosis risk has been reported for both conditions in Fontan patients.Copyright © 2023 American College of Cardiology Foundation
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Objetivo: Avaliar se os marcadores de endoteliopatias continuamente elevados apos a alta hospitalar por COVID-19 possui correlacao com o tempo de internacao dos pacientes. Materiais e Metodos: Foram recrutados 97 pessoas sobreviventes de COVID-19 com a infeccao confirmada pelo ensaio de RT-PCR (PCR real time) de 18 a 65 anos internadas na unidade de terapia intensiva de dois grandes hospitais de referencia regionais. Os voluntarios dos tres grupos estavam curados ha pelo menos 30 dias da convocacao. Todos assinaram o Termo de Consentimento Livre Esclarecido (TCLE) e a pesquisa foi aprovada pelo Comite de Etica da Universidade Federal do Espirito Santo, sob numero CAAE 37094020.6.0000.5060. A infeccao pelo SARS-CoV-2 precedeu a vacinacao completa dos pacientes estudados (considerando 2 doses minimas). Os participantes responderam um formulario no RedCap e os dados relacionados a internacao foram adquiridos junto aos hospitais. Foram analisados dois marcadores que podem indicar a endoteliopatia: Fator de von Willebrand Antigeno (FvW:Ag) e D-dimero (DD). O teste de multipla regressao linear foi usado para estabelecer a diferenca entre o tempo de internacao e os parametros avaliados e foi considerado significativa p < 0,05. Resultados: Pacientes com o FvW:Ag e FVIII >150% apos a alta tiveram a media do tempo de internacao de 12 dias e mediana de 10 dias, em contrapartida, pacientes com niveis normais de FvW:Ag e FVIII internaram em media 10 dias e a mediana foi de 8 dias, p=0,0536 e p=0,1539 respectivamente. Os pacientes com o DD >500 mg/dL apos a alta tiveram a media do tempo de Internacao de 11,6 dias e mediana de 10 dias, os pacientes com niveis normais de DD internaram em media 10,75 dias e a mediana 8 dias, p < 0,0001. Discussao: Os marcadores de endoteliopatias FvW:Ag, FVIII e DD demonstraram em um estudo anterior desse mesmo grupo de pesquisa diferenca significativa quando comparados ao grupo controle de participantes que tambem tiveram COVID-19 a nivel ambulatorial (p < 0,05), indicando que esses marcadores permanecem alterados significantemente em pacientes que internaram na UTI apos a alta hospitalar. Varios estudos apontaram os marcadores avaliados nesse trabalho como possivelmente alterados na fase aguda da COVID-19, predizendo a forma grave da doenca. Nao foi estabelecido apos uma analise multivariada uma correlacao entre o FvW:Ag e FVIII continuamente alterados apos a alta hospitalar e o tempo em que os pacientes ficaram internados. Entretanto, o DD alterado apos a alta demonstrou correlacao positiva com o aumento do tempo de internacao dos pacientes, corroborando com outros estudos. Conclusao: A endoteliopatia por infeccao endotelial direta com SARS-CoV-2 e os danos indiretos causados pela inflamacao desempenham o papel predominante no desenvolvimento e agravamento da COVID-19. As consequencias do desbalanceamento do sistema pro e anti trombotico estao relacionados com o tempo de internacao dos pacientes. A COVID-19 longa, na fase pos-aguda, e uma sindrome caracterizada pela persistencia dos sintomas clinicos alem de quatro semanas do inicio dos sintomas agudos e pode estar associada a resquicios da endoteliopatia causada pela infeccao. Copyright © 2022
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Introducao: A hemofilia A (HA) e uma doenca hemorragica caracterizada pela ocorrencia de sangramentos, principalmente articulares e musculares. Embora esses pacientes sejam considerados relativamente protegidos de eventos tromboticos, existem relatos de trombose venosa, associada a fatores de risco como pos-operatorio ou com reposicao de fator. Relato de caso: Homem, 22 anos, em seguimento no Hemocentro de Ribeirao Preto com diagnostico de HA grave sem inibidor em profilaxia com fator VIII recombinante (FVIIIR). Compareceu para avaliacao em marco de 2022 com queixa de dor e edema difuso na perna direita iniciados ha 10 dias, sem historia de trauma associado. No inicio do quadro clinico, o paciente nao procurou atendimento medico e realizou reposicao de FVIIIR diariamente, com dose superior a habitual (elevacao de FVIII em 50%), conforme julgamento pessoal e sem definicao diagnostica. Como nao apresentou melhora clinica, no decimo primeiro dia de evolucao, procurou atendimento e, apos avaliacao clinica, foi aventada a hipotese de hematoma muscular no compartimento posterior da perna direita, sendo optado pela manutencao do esquema de reposicao diaria, repouso muscular e reavaliacao em 72 horas. Na reavaliacao, paciente mantinha quadro clinico, realizada Tomografia Computadorizada, que nao identificou sangramento muscular. Nesse contexto, foi optado por realizacao de Doppler Venoso de membro inferior direito, que evidenciou tromboflebite de veia safena parva medindo cerca de 10 cm, estendendo-se do terco proximal ate o terco medio da perna, sem acometer o sistema venoso profundo. O hemograma nao evidenciava plaquetopenia. Como potencial fator de risco adicional, o paciente referiu ter recebido a 3degreedose da vacina para COVID19 (AstraZeneca) cerca de 3 semanas antes do inicio dos sintomas. Por se tratar de tromboflebite extensa, com repercussoes clinicas, caracterizadas por comprometimento funcional do membro, o paciente teria indicacao de anticoagulacao terapeutica. Porem, considerando contexto clinico e doenca de base, optamos por manter observacao clinica, repouso, medidas locais, reducao da reposicao de FVIIIR e repeticao do Doppler precocemente. O exame de controle com intervalo de 4 semanas mostrou recanalizacao completa da veia safena parva, bem como houve remissao completa dos sintomas e recuperacao funcional do membro acometido. Discussao: Apesar de ser uma complicacao rara, deve ser considerada, especialmente em casos que apresentem refratariedade clinica, como a situacao apresentada. Particularmente nesse caso, ha de se considerar o fato do paciente ter recebido a vacina para COVID19 anteriormente ao quadro, cuja associacao com quadros de trombose e plaquetopenia vem sendo descrito na populacao em geral, porem os dados sao escassos em paciente com coagulopatias. Ademais, estes pacientes pela "anticoagulacao natural", inerente a patologia de base, podem nao apresentar quadros tao floridos e graves quanto os descritos na literatura. Nao ha como se definir com precisao a contribuicao da reposicao de fator iniciada pelo paciente em regime domiciliar (doses maiores e de forma mais intensa) no desenvolvimento do quadro atual. Conclusao: Eventos tromboticos nessa populacao, apesar de raros, podem ocorrer, e, a decisao quanto a anticoagulacao e desafiadora. E importante avaliar os potenciais fatores de risco associados como traumas, cirurgias e, no contexto atual, a associacao com a vacina para COVID19. Copyright © 2022
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Background and Aim: Cardiovascular manifestations are common (35-100%) in multisystem inflammatory syndrome in children (MIS-C), including ventricular dysfunction, shock, coronary artery dilation, pericardial effusion and conduction abnormalities. Our study aimed to analyse cardiovascular involvement in our patients with MIS-C treated in our hospital. Method(s): The retrospective cohort study included all patients with MIS-C treated from April 2020 to December 2021 in the Mother and Child Health Institute of Serbia. In every case, cardiovascular manifestations were analysed: ventricular dysfunction, coronary artery dilatation, pericardial effusion, shock and ECG changes. Result(s): The study included 77 patients, 45 boys and 32 girls, aver-age years of age 9.3 +/- 4.8. Elevated cardiac troponin I and pro-BNP were observed in 35.9% and 87.8% of patients, respectively. Myocardial dysfunction was observed in half of our patients (50.6%), with an average ejection fraction of 50.5 +/- 8.9%. Children older than 10 years had 4 times higher chances for myo-cardial dysfunction (OR 4.3, 95%CI 1.6-10.8;p = 0.003). Shock syndrome had 21.1% of children on admission, while 5.3% devel-oped shock during the in-hospital stay. Transient coronary artery (CA) dilatation was observed in 6.5% of patients;left CA in 3 pts (Z score +2,95 +/- 0.3), right CA in one patient (Z score +2), and in one LCA and RCA (RCA Z score 2.6). Transient CA dilatations were observed only in patients with KD-like clinical presentation (5/54 pts). Mild pericardial effusion with spontaneous resolution was detected in 28.6% of children, while one female adolescent had severe pericardial effusion with threatening cardiac tamponade. On the standard ECG, 53% of children had negative T wave in inferior or/and precordial leads averagely on day 2 (IQR 1-3 day);transient QTc prolongation was registered in 46% of patients, averagely on day 7 (IQR 5-9). Sinus bradycardia and coronary rhythm were registered in 42.1% of patients, while premature ven-tricular beats were observed in 2.7% of pts. left ventricle thrombus was detected in one patient with normal echocardiography find-ing. In this patient, increased activity of Factor VIII and XII was proven. Conclusion(s): Cardiac manifestations are common and potentially life-threatening in MIS-C and should be assessed for at presenta-tion and during the clinical course as indicated.
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SESSION TITLE: Rare Cases of Nervous System and Thrombotic Complication Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Covid 19 virus has impacted nearly 450 million people across the globe;ranging from an asymptomatic carrier state to respiratory symptoms, cardiovascular symptoms, hematologic manifestations and multiorgan failure to death. Thrombotic events are one of its devastating complications. CASE PRESENTATION: A 66 year old man with a history of diabetes mellitus, hypertension and 30 pack years smoking history presented to the emergency room with hypoxia and altered mental status. On exam, his GCS was 8/15 and oxygen saturation was 85% on room air. He was subsequently intubated. CTA chest demonstrated bilateral diffuse ground glass opacities and left pulmonary embolism (PE). CT abdomen and pelvis showed multifocal infarcts in the right kidney with findings suggestive of renal artery thrombosis. Initial platelet count was 80,000/ul with creatinine of 3.9 mg/dl and creatine kinase (CK) of 3977 u/l. His INR was 1.4. Patient was not a candidate for thrombolysis given his thrombocytopenia. He was started on intravenous (IV) heparin and given IV hydration. On day 3 of his admission, he developed dry gangrene of the toes. Ankle brachial index of the right lower extremity (LE) was 1.16 and left LE was 0. Duplex ultrasonography of left LE showed mid to distal popliteal artery thrombus occluding below knee popliteal and tibial arteries. Echocardiogram showed ejection fraction of 55% and bubble study was negative for any intra atrial or pulmonary shunting. On day 4 of his admission, he developed oliguria and his gangrene got worse. His platelet counts decreased to 36,000/ul. Other pertinent labs showed INR 1.2, PT 15.3, PTT 34, D dimer 14.82, fibrinogen 498, CK 6434 mg/dl, hemoglobin 13.2 g/dl, haptoglobin 243 mg/dl and LDH 1041 U/l. Given his poor prognosis in the setting of ventilator dependent respiratory failure, multiple thrombosis and kidney failure requiring hemodialysis, the family decided to withdraw care. DISCUSSION: There are multiple hypotheses of thrombus formation in Covid 19 infection such as interleukin 6 and other cytokines induced endothelial injury, angiogenesis and elevated prothrombotic factors such as factor VIII and fibrinogen. Our patient had PE, renal artery thrombosis and popliteal artery thrombosis. Despite being on full dose anticoagulation, he developed gangrene of the toes. His lab results were not consistent with disseminated intravascular coagulation, thrombotic thrombocytopenic purpura and he was not known to have any baseline hypercoagulable disorder. He did not have any intra cardiac shunts. Hence, it is most likely Covid 19 induced multiple arterial and venous thrombosis. CONCLUSIONS: The treatment of Covid 19 related thrombosis has become very challenging especially in the setting of multiple clots. It is crucial to have large multicenter studies to investigate vascular complications of Covid-19 and to formulate management strategies to ensure good patient outcomes. Reference #1: https://www.nejm.org/doi/full/10.1056/nejmoa2015432 Reference #2: https://journal.chestnet.org/article/S0012-3692(21)01126-0/fulltext DISCLOSURES: No relevant relationships by Devashish Desai No relevant relationships by Swe Swe Hlaing no disclosure on file for Jean Marie Koka;No relevant relationships by Hui Chong Lau No relevant relationships by Subha Saeed No relevant relationships by Anupam Sharma No relevant relationships by Muhammad Moiz Tahir
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Background: SARS-COV2 infection is associated with inflammation, hypercoagulability and endothelial damage. Anti-SARS-COV2 vaccines have radically changed the course of the pandemic, however, reports on rare thrombotic events raise concern in the scientific community and the general population. Aims: In a prospectively enrolled cohort of adult subjects undergoing mRNA or adenovirus vector vaccination, we wanted to longitudinally evaluate the changes in levels of hemostatic biomarkers (i.e. activation of blood coagulation and perturbance of endothelium and fibrinolysis), together with the serological response, and occurrence of manifest thrombotic complications. Methods: Peripheral venous blood samples were collected at enrollment (day 0, D0) before the 1st vaccine dose, and on 15 (D15), 60 (D60), 90 (D90) and 180 (D180) days after the 1st dose. At each time point, hemostatic markers (i.e., fibrinogen, D-dimer, FVIII, von Willebrand Factor [vWF] antigen and activity, F1+2, thrombomodulin, protein C, protein S, FXIII, tPA, and PAI-1), and anti-Spike receptor-binding-domain protein (anti-S/RBD) IgG were measured. Follow up is currently continuing. Results: Fifty-three subjects (57% males) with a median age of 50 years (range 23-86) were enrolled into the study and followed-up for 6 months: 36 (68%) received BNT162b2, 6 (11%) mRNA-1273, and 8 (15%) ChAdOx1 nCoV-19 vaccines, in 2 doses over 21, 30 and 77 days, respectively;while 3 (6%) subjects received Ad26.COV2.S as single shot. Twenty individuals (38%) reported previous history of COVID-19, with a mean time from infection to vaccination of 10 months (4-18);only 1 required Hospitalization. Nine subjects presented cardiovascular risk factors and 4 a prior, non-active, cancer;3 were on anticoagulation for atrial fibrillation. The evaluation of the hemostatic biomarkers at the different time points showed variations in some of the parameters evaluated, with median values remaining within normal range levels. Specifically, compared to baseline, we observed a significant increase in thrombomodulin at D90 (p=0.001) and D180 (p=0.03), in parallel to a significant decrease in fibrinogen (D60), vWFAg (D60 and D180), FVIII (D60, D90 and D180), and TPA (D60 and D90) levels. The reduction of these biomarkers was particularly evident in individuals with a history of COVID-19. Of interest, this group of subjects was also characterized by significantly lower levels of PAI-1 both at baseline (7.18 ng/mL vs 17.53 ng/mL;p<0.0001), and at other time points (p<0.0001), and by an increase in F1+2 at D90 (p=0.02). The association between lower baseline PAI-1 levels with history of COVID-19 was confirmed by linear regression analysis (B= -10.351, p=0.013), and was independent by the time of infection resolution. Notably, no differences were observed in the hemostatic biomarkers according to vaccine types. All subjects positively responded to vaccination with a significant increase in anti-S/RBD IgG from baseline (D0) to each time point, especially COVID-19 subjects (D15, D60, and D90:p<0.0001;D180:p=0.031). No thrombotic or cardiovascular complications occurred during follow-up. Summary/Conclusion: No hypercoagulable state elicited by COVID-19 vaccination was observed, contrarily we detected an overall persistent reduction of coagulation activation over time. Subjects with previous SARS-COV2 infection had persistently low levels of PAI-1, supporting enhanced fibrinolysis activation. Compared with recent studies, our results provide a longer observation follow-up with all vaccine types and reassure on the safety of anti- SARS-COV2 vaccination.
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Background: The polymorphism C>T substitution in position 677 (C677T) of the encoding gene of methylenetetrahydrofolate reductase (MTHFR), creates a thermolabile enzyme with reduced activity that may predispose to hyperhomocysteinemia , an established risk factor for arterial thrombosis and premature atherosclerosis and a probable risk factor for venous thromboembolic disease and its recurrence in the general population. There are conflicting results as to the role of the MTHFR C677T polymorphism as a risk factor for thrombosis. Although the homozygous substitution is often associated with hyperhomocysteinemia, mainly in folate deficiency, a clear association between this genetic marker and thrombosis has not yet been established. Aims: Primary aim was to evaluate the prevalence of mutant C677T MTHFR and its association with thrombosis in the Greek paediatric population. Secondary aim was to evaluate whether different MTHFR genotype is associated with evidence of activation of coagulation cascade through increased factor VIII activity. Methods: Data were retrospectively collected from children referred to our Haemostasis and Thrombosis Centre for laboratory screening of thrombophilia between 2018 and 2020. Some of them were checked due to history of thrombosis. Children were categorized according to MTHFR C677T genotype. FVIII Coagulant activity (%) was measured by One Stage Assay, away from acute thrombosis. The identification of mutations was based on polymerase chain reaction (PCR) and reverse- hybridization. Statistical analysis was performed with t-test and ANOVA. Results: A total of 688 children (boys: 49 %) of mean age 8.9± 8 years (0-18) were investigated. Twelve percent (81/688) of them had history of thrombosis, mainly venous thromboembolic disease. Children were categorized as follows: homozygous MTHFR C677T (15%), heterozygous (47%) and normal (38%). There was thrombosis history in 12% of homozygous MTHFR C677T, 11% heterozygous and 12 % of normal, fact showing that there is no association between MTHFR C677T genotype with thrombosis. Children with homozygosity MTHFR C677T, compared to children with heterozygosity and normal MTHFR C677T showed increased factor VIII values (132.8 vs 126.4 and 131.6, %, respectively), but without statistically significant difference. However, independently of MTHFR C677T genotype, mean factor VIII values were significantly increased in all children, with thrombosis history when they were compared to children without thrombosis history (161.3 vs 125.1, %, p<0.001). Interestingly, in children with thrombosis, mean factor VIII level was statistically increased in heterozygous and normal MTHFR C677T in contrast to children with MTHFR C677T homozygosity, in whom no statistically significant increase was found (166.9 vs 121.4, %-p<0.05, 160.2 vs 127.6, %-p<0.05 and 148.3 vs 130.6, %-p>0.05, respectively). Finally, it should be noticed that during the year 2020 mean factor VIII values were much increased in all children in comparison to the years 2018, 2019 and 2021 (137 vs 129, 123 and 127, %, respectively), probably reflecting the effects of unknown pandemic COVID-19 which initiated in 2020, and showing that factor VIII could be an evidence of stress condition. Summary/Conclusion: There is no probably association between MTHFR C677T genotype and thrombosis in our paediatric population. Moreover, it was not proved that different MTHFR genotypes affect factor VIII activity.
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Introduction Cerebral venous thrombosis (CVT) may occur due to a number of common etiologies such as thromboembolism, atherosclerotic disease, or small vessel disease. When these are ruled out or considered unlikely, a hypercoagulability workup is performed. We describe a series of 30 patients with CVT and medical and/or genetic basis for the underlying hypercoagulable state and thrombophilia. Methods A retrospective review of all CVT cases treated with venous thrombectomy between June 2016 and August 2021 was performed within our institutional, neuroendovascular database. Results Of the 30 patients identified, 18 were associated with a hypercoagulable state and/or thrombophilia. Underlying illness was present in seven (36.8%) patients due to polycythemia vera, systemic lupus erythematosus, a combination of nephrotic syndrome and morbid obesity, a combination of rheumatoid arthritis and diabetes, chronic rejection of a small bowel transplant further complicated by acute renal failure and ARDS, a combination of diabetes, DVT, and a dyslipidemic state, and Covid-19. Hypercoagulable states were identified in seven (36.8%) patients due to elevated Factor VIII (1/ 7), antiphospholipid syndrome (3/7), and Protein S deficiency (3/7). Genetic thrombophilia was identified in four (16.4%) patients in the form of a heterozygous Factor V mutation in R506Q (2/4), a heterozygous Prothrombin Factor II mutation in G20210A (1/4), and a homozygous 4G/4G promoter Plasminogen Activator inhibitor I deletion mutation (1/4). Overall, no subset of hypercoagulability (I.e. mutation, disease, transient state) nor hypercoagulability overall was predictive of outcome as measured by recanalization, discharge disposition, or reocclusion likelihood. Conclusion The most common cause of hypercoagulability was underlying disease or transient antiphospholipid syndrome/elevated pro-coagulation factor. While we are unable to report hypercoagulability as a predictive variable of outcome in our cohort, we outline the presence of various coagulopathies within this medically refractory, CVT cohort. While CVT may occur due to many common pathologies, in cases where the cause is unknown a hypercoagulability workup my shed light on mitigating factors underlying the thrombosis.
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The relevance of coagulation malfunction in COVID-19 (severe coronavirus disease) is ambiguous. Current study aimed to assess the coagulation among SARS-CoV-2 hospitalized patients. A cross sectional study with qualitative approach was conducted among 300 patients who are already diagnosed as COVID 19 compared to 300 apparently healthy control group attended to Red Sea State during study period from April 2020 to April 2021. The Humaclot Due Plus1 coagulation analyser was used to estimate the prothrombin time (PT), activated partial prothrombin time (APTT), and international normalized ratio (INR) (Wiesbaden 1, Germany), adding 25 μL of plasma in cuvette. The study result showed that in COVID-19 patients D.dimer level is high (2000-10000 ng/mL) compared with control group (up to 500 ng/mL). COVID-19 infection cause high D. dimer level which can lead to thrombosis event or bleeding tendency. Abnormal coagulation results were revealed among SARS-CoV-2, with markedly elevated D. dimer.
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Background: Infections, drugs, surgical procedures, blood transfusions, solid and hematological cancers, and autoimmune disorders are associated with the risk of developing acquired FV inhibitors. Case report presentation: A 66-year-old Caucasian woman presented to the Emergency Department because of recurrent episodes of bowel bleeding from 2 week, and bleeding from the sites of venous sampling. Coagulation tests showed that the platelet count was normal: prolonged prothrombin time (PT): 45.5 seconds, international normalized ratio: 4.03, and activated partial thromboplastin time (aPTT): 165 seconds, aPTT ratio: 5.4. Coagulation factor II (FII), factor X (FX), factor VIII (FVIII), and fibrinogen were normal. The FV activity was 0.2% (range of normality 60-120%). The PT, aPTT, and one-stage coagulation factors assays were performed using an ACL TOP 550 coagulometer, and factor V was determined using a onestage PT-based assay, and factor V-deficient substrate plasma. Anticardiolipin antibodies were negative. Mixing test of patient's plasma with normal pooled plasma revealed the existence of an FV inhibitor, with an activity level of 4.0 Bethesda unit/mL. Three weeks before, the patient had been treated for coronavirus disease 2019 (COVID- 19) at home, with steroids (dexamethasone 6 mg daily for 5 days), enoxaparin 4,000 IU daily, and oxygen. Conclusions: The Authors presented a case report with acquired factor V inhibitor after SARS-CoV2 disease.