Fresh frozen plasma transfusion in patients with cirrhosis and coagulopathy: Effect on conventional coagulation tests and thrombomodulin-modified thrombin generation.

BACKGROUND & AIMS: The efficacy of fresh frozen plasma (FFP) transfusion in enhancing thrombin generation in patients with cirrhosis and impaired conventional coagulation tests has not been sufficiently explored. Thus, we aimed to assess the effect of FFP transfusion on thrombin generation in these patients. METHODS: Fifty-three consecutive patients receiving a standard dose of FFP to treat bleeding and/or before invasive procedures - if international normalized ratio (INR)/prothrombin time (PT) ratio were ≥1.5 - were prospectively enrolled. The primary endpoint was the amelioration of endogenous thrombin potential (ETP) with thrombomodulin (ETP-TM) after transfusion, which corresponds to the total amount of generated thrombin. INR/PT ratio and activated partial thromboplastin time (aPTT) were also assessed before and after transfusion. RESULTS: FFP enhanced ETP-TM by 5.7%, from 973 (731-1,258) to 1,028 (885-1,343 nM × min; p = 0.019). Before transfusion, evidence of normal or high ETP-TM was found in 94% of patients, even in those with bacterial infections. Only 1 (1.9%) patient had ETP-TM values reverting to the normal range after transfusion. Notably, no patients with low ETP-TM had bleeding. The median decrease in ETP-TM was 8.3% and the mean was 12.8% in 18 (34%) patients after transfusion (from 1,225 [1,071-1,537] to 1,124 [812-1,370] nM × min; p ≤0.0001). Similar responses to FFP transfusion were observed in patients with compensated and acute decompensated cirrhosis, acute-on-chronic liver failure, infection or shock. FFP significantly ameliorated INR and aPTT values (p <0.0001), but in a minority of patients the values were reduced to less than the cut-off point of 1.5. CONCLUSIONS: FFP transfusion enhanced thrombin generation and ameliorated conventional coagulation tests to normal values in a limited number of patients, and slightly decreased thrombin generation in 34% of cases. LAY SUMMARY: Transfusion of fresh frozen plasma in patients with cirrhosis only slightly improves coagulation test values in a limited number of patients and even appears to worsen them in a third of cases. Transfusion for the purpose of preventing or treating bleeding events could cause inherent risks and costs without clear benefits.

Preservation of platelet function in patients with cirrhosis and thrombocytopenia undergoing esophageal variceal ligation.

BACKGROUND: Thrombocytopenia is a possible risk factor for bleeding after band ligation of esophageal varices. However, elevated von Willebrand factor (VWF) in cirrhosis improves platelet function and could decrease this risk. Our objective was to assess platelet function in patients with cirrhosis undergoing esophageal variceal ligation (EVL). METHODS: The assessment consisted of platelet count, antigen and activity of VWF and VWF-cleaving protease ADAMTS-13 activity, and a platelet adhesion and aggregation test simulating vascular flow in vivo (Impact-RⓇ) prior to EVL. RESULTS: Totally 111 patients were divided into three groups according to platelet count: (1) < 50 × 109/L (n = 38, 34.2%); (2) 50 × 109/L to 100 × 109/L (n = 47, 42.3%); and (3) > 100 × 109/L (n = 26, 23.4%). No statistically significant difference was found in the aggregate size of platelets [group 1: 41.0 (31.8-67.3) µm2; group 2: 47.0 (33.8-71.3) µm2; and group 3: 47.0 (34.0-66.0) µm2; P = 0.60] and no significant correlation was found between aggregate size and platelet count (Spearman r = 0.07; P = 0.47). Surface coverage was 4.1% (2.8%-6.7%), 8.5% (4.0%-10.0%), and 9.0% (7.1%-12.0%) (P < 0.001) in groups 1, 2 and 3, respectively and correlated with platelet count (Spearman r = 0.39; P < 0.0001). There was no significant difference between groups in VWF or ADAMTS-13. Post-EVL bleeding occurred in six (5.4%) patients (n = 2 in group 1, n = 1 in group 2, and n = 3 in group 3; P = 0.32). Patients with bleeding had higher MELD scores [15.0 (11.3-20.3) versus 12.0 (10.0-15.0); P = 0.025], but no difference was demonstrated for platelet function parameters. CONCLUSION: Platelet function is preserved even in the presence of thrombocytopenia, including in the patients with post-EVL bleeding.

Arthroscopic partial anterior synovectomy of the knee on patients with haemophilia.

PURPOSE: This study assessed the results of two-portal knee arthroscopic synovectomy in terms of bleeding recurrence, knee function, quality of life (QOL), and radiographic staging in a prospective case series of patients with haemophilia. METHODS: Nine knees from eight patients (median age 16.1 years; range 9.6-25 years) with haemophilia and recurrent knee haemarthrosis were prospectively evaluated. Yearly recurrence of bleeding was evaluated once a year for 5 years postoperatively. Range of motion (ROM) and radiographic staging, as well as results of the short form (SF)-36 and subjective knee form of the International Knee Documentation Committee (IKDC) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaires, were evaluated before surgery and at the end of follow-up. RESULTS: Mean bleeding recurrence was significantly reduced during the 5-year follow-up period. Questionnaire results showed significant improvements (IKDC P = 0.015, WOMAC P = 0.011, and SF-36 P = 0.023), whereas ROM was not significantly affected. Arthropathy progressed from Arnold-Hilgartner radiographic stage III to stage IV (P = 0.0082). CONCLUSIONS: Two-portal knee arthroscopic synovectomy was effective at reducing bleeding recurrence and improving knee function and QOL in patients with haemophilia, but did not interrupt the progression of radiographic changes.

Aspirin responsiveness safely lowers perioperative cardiovascular risk.

INTRODUCTION: Vascular surgeries are related to high cardiac morbidity and mortality, and the maintenance of aspirin in the perioperative period has a protective effect. The purpose of this study was to evaluate the association between preoperative platelet aggregability and perioperative cardiovascular (CV) events. METHODS: A preoperative platelet aggregation test was performed on an impedance aggregometer in response to collagen and to arachidonic acid (AA) for 191 vascular surgery patients under chronic use of aspirin. We analyzed the following CV events: acute myocardial infarction, unstable angina, isolated troponin elevation, acute ischemic stroke, reoperation, and cardiac death. Hemorrhagic events were also evaluated and classified according to the Thrombolysis In Myocardial Infarction criteria. RESULTS: The incidence of CV events was 22% (n = 42). Higher platelet response to AA was associated with CV events, so that patients in the fourth quartile (higher than 11Ω) had almost twice the incidence of CV events when compared with the three lower quartiles: 35% vs 19%; P = .025. The independent predictors of CV events were hemodynamic instability during anesthesia (odds ratio [OR], 4.12; 95% confidence interval [CI], 1.87-9.06; P < .001), dyslipidemia (OR, 3.9; 95% CI, 1.32-11.51; P = .014), preoperative anemia (OR, 2.64; 95% CI, 1.19-5.85; P = .017), and AA platelet aggregability in the upper quartile (OR, 2.48; 95% CI, 1.07-5.76; P = .034). Platelet aggregability was not associated with hemorrhagic events, even when we compared the lowest quartile of AA platelet aggregability (0-1.00 Ω) with the three upper quartiles (>1.00 Ω; OR, 0.77; 95% CI, 0.43-1.37; P = .377). CONCLUSIONS: The degree of aspirin effect on platelet aggregability maybe important in the management of perioperative CV morbidity, without increment in the bleeding toll.

Immunogenicity, long term protection and safety of subcutaneous administration of hepatitis A vaccine in patients with hemophilia and other bleeding disorders: A randomized study.

Hepatitis A vaccine is recommended for all individuals with hemophilia, although patients with bleeding disorders should avoid intramuscular (IM) injections. To date, only few studies showed subcutaneous (SC) route immunogenicity is comparable with the IM route. Therefore, this randomized study compared immunogenicity, long term protection and safety of hepatitis A vaccine administered by SC route with the IM route in 78 children and adults with hemophilia and other bleeding disorders. Thirty-eight patients had serology performed after first vaccine dose, determining seroconversion rates of 83.3% and 90.0% for the SC and the IM group, respectively (p = 0.5). Median IgG CO/OD value for the SC group was almost the double compared with the IM group (4.4 vs 2.6, p = 0.2). After second vaccine dose, seroconversion rates for the SC group was 97.5% and for the IM group was 97.4% (p = 1.0). Of the two patients who did not have seroconversion, interval between vaccine dose and serology was only one and two days for the SC and the IM group, respectively and in the following routine antibody dosage they presented seroconversion (100% for both groups). Median IgG CO/OD value for the SC group was greater than the IM group (72.5 vs. 58.0, p = 0.2). In a median of nine years after second vaccine dose, median IgG S/CO value for the SC group was slightly greater than the IM group (7.6 vs. 7.4, p = 0.8). There were no serious adverse events in both groups. Five (12.5%) patients of the SC group and seven (18.4%) of the IM group presented adverse events (p = 0.5). Twice as many patients of the IM group had clotting factor concentrates need for adverse events (15.8% vs. 7.5%, p = 0.3). Therefore, hepatitis A vaccine administered subcutaneously is as immunogenic, long term protective and even safer than the intramuscular route.

Heparin Therapy Improving Hypoxia in COVID-19 Patients - A Case Series.

INTRODUCTION: Elevated D-dimer is a predictor of severity and mortality in COVID-19 patients, and heparin use during in-hospital stay has been associated with decreased mortality. COVID-19 patient autopsies have revealed thrombi in the microvasculature, suggesting that hypercoagulability is a prominent feature of organ failure in these patients. Interestingly, in COVID-19, pulmonary compliance is preserved despite severe hypoxemia corroborating the hypothesis that perfusion mismatch may play a significant role in the development of respiratory failure. METHODS: We describe a series of 27 consecutive COVID-19 patients admitted to Sirio-Libanes Hospital in São Paulo-Brazil and treated with heparin in therapeutic doses tailored to clinical severity. RESULTS: PaO2/FiO2 ratio increased significantly over the 72 h following the start of anticoagulation, from 254(±90) to 325(±80), p = 0.013, and 92% of the patients were discharged home within a median time of 11 days. There were no bleeding complications or fatal events. DISCUSSION: Even though this uncontrolled case series does not offer absolute proof that micro thrombosis in the pulmonary circulation is the underlying mechanism of respiratory failure in COVID-19, patient's positive response to heparinization contributes to the understanding of the pathophysiological mechanism of the disease and provides valuable information for the treatment of these patients while we await the results of further prospective controlled studies.

A prospective study of conventional and expanded coagulation indices in predicting ulcer bleeding after variceal band ligation.

BACKGROUND & AIMS: There is controversy over whether coagulation status predicts bleeding caused by ulceration after esophageal varices band ligation (EVL). METHODS: EVL was performed for primary (n = 45) or secondary (n = 105) prophylaxis in 150 patients with cirrhosis (Child A, n = 74, 49%; Child B, n = 42, 28%; Child C, n = 34, 23%). International normalized ratio (INR) and platelet counts were assessed in all. In 92 patients, levels of factor V, fibrinogen, D-dimer, protein C and protein S, von Willebrand factor, and thromboelastography (TEG) were assessed. Platelet count <50 x 10(3)/mm(3) and INR >1.5 were considered high-risk cutoff for bleeding. Conversely, platelet count >or=50 x 10(3)/mm(3) with INR

Estrogen treatment improves arterial distensibility, fibrinolysis, and metabolic profile in postmenopausal women with type 2 diabetes mellitus.

The effects of isolated estrogen therapy on the hemostatic system and arterial distensibility were determined in postmenopausal females with type 2 diabetes mellitus. This was a prospective nonrandomized study of 19 subjects (age, 56.2 +/- 4.7 years; body mass index, 27.8 +/- 2.4 kg/m(2) [mean +/- SD]). Inclusion was done after 2 months of glycemic and blood pressure control. The study consisted of 4 months of placebo treatment immediately followed by an equal period of oral conjugated equine estrogens (CEE) 0.625 mg/d. Measures included anthropometrics, a metabolic profile (oral glucose tolerance test and fasting glycated hemoglobin, total cholesterol and fractions, and triglyceride levels), and coagulation and fibrinolytic factors at the end of the placebo period and after 4 months of oral CEE. Conjugated equine estrogen therapy decreased plasminogen activator inhibitor 1 (placebo x CEE: 16.33 +/- 9.11 x 13.08 +/- 8.87 UI/mL, P < .03) and increased factor VIII activity (134.11% +/- 46.18% x 145.33% +/- 42.04%, P < .04). An increase in high-density lipoprotein cholesterol levels (placebo x CEE: 42.47 +/- 6.80 x 53.32 +/- 11.89 mg/dL, P < .01), and a decrease in glycated hemoglobin (8.45% +/- 1.30% vs 7.58% +/- 1.06%, P < .02) and in fasting glucose levels (121.51 +/- 21.05 x 111.21 +/- 20.74 mg/dL, P = .02) followed CEE therapy. Pulse wave velocity and augmentation index were performed by applanation tonometry and were obtained at the end of the placebo period (placebo), again after an intravenous load of 1.25 mg of CEE (short-term), and after 4 months of oral CEE (long-term). A significant decrease in central (carotid-femoral) pulse wave velocity was seen both after short- and long-term CEE (placebo vs short-term vs long-term: 9.36 +/- 2.58 vs 8.26 +/- 2.20 vs 7.98 +/- 1.90 m/s, respectively [analysis of variance, P < .03]; placebo vs short-term, P < .05; placebo vs long-term, P < .01), whereas augmentation index decreased only after long-term CEE (placebo vs short-term vs long-term: 39.14% +/- 6.94% vs 37.48% +/- 8.67% vs 34.3.3% +/- 8.11% [analysis of variance, P < .05], respectively; placebo vs long-term, P < .05). Long-term administration of CEE leads to an improvement in fibrinolysis and arterial distensibility, associated with an increase of the intrinsic coagulation pathway in postmenopausal women with type 2 diabetes mellitus.

Branch retinal vein thrombosis and visual loss probably associated with pegylated interferon therapy of chronic hepatitis C.

Ophthalmological complications with interferon therapy are usually mild and reversible, not requiring the withdrawal of the treatment. We report a case of a patient who had visual loss probably associated with interferon therapy. Chronic hepatitis C virus infection (genotype 1a) was diagnosed in a 33-year old asymptomatic man. His past medical history was unremarkable and previous routine ophthalmologic check-up was normal. Pegylated interferon alpha and ribavirin were started. Three weeks later he reported painless reduction of vision. Ophthalmologic examination showed extensive intraretinal hemorrhages and cotton-wool spots, associated with inferior branch retinal vein thrombosis. Antiviral therapy was immediately discontinued, but one year later he persists with severely decreased visual acuity. This case illustrates the possibility of unpredictable and severe complications during pegylated interferon therapy.

Drug Interaction Between Clopidogrel and Ranitidine or Omeprazole in Stable Coronary Artery Disease: A Double-Blind, Double Dummy, Randomized Study.

BACKGROUND: Proton-pump inhibitors (PPIs) are often prescribed to patients receiving dual antiplatelet therapy (DAPT). However, this class of medication, especially omeprazole, has been associated with a reduction in clopidogrel efficacy, leading many clinicians to substitute omeprazole with ranitidine. OBJECTIVES: Our objective was to compare the antiplatelet effect of clopidogrel before and after the addition of omeprazole or ranitidine. METHODS: We measured platelet aggregability at baseline and after 1 week of clopidogrel 75 mg daily. Subjects were then randomized in a double-blinded, double-dummy fashion to omeprazole 20 mg twice daily (bid) or ranitidine 150 mg bid. We repeated aggregability tests after 1 additional week, using VerifyNow P2Y12™ (Accumetrics; San Diego, CA, USA), depicting aggregability as percent inhibition of platelet aggregation (IPA). RESULTS: We enrolled 41 patients in the omeprazole group and 44 in the ranitidine group. IPA was significantly decreased after the addition of omeprazole to clopidogrel (from 26.3 ± 32.9 to 17.4 ± 33.1 %; p = 0.025), with no statistical significant changes observed in the ranitidine group (from 32.6 ± 28.9 to 30.1 ± 31.3 %; p = 0.310). The comparison of IPA in both groups at the end of the follow-up showed a trend toward significance (p = 0.07, 95 % confidence interval [CI] -1.19 to 26.59); after excluding homozygous patients for 2C19*2 genotype, the comparison of IPA between the groups reached statistical significance (32.7 ± 30.8 vs. 17.7 ± 33.4 %, respectively, for ranitidine and omeprazole groups; p = 0.04). CONCLUSIONS: Unlike omeprazole, ranitidine did not influence platelet aggregability response to clopidogrel. CLINICAL TRIAL REGISTRATION: NCT01896557.

Successful management of neonatal alloimmune thrombocytopenia in the second pregnancy: a case report.

Neonatal alloimmune thrombocytopenia is a serious disease, in which the mother produces antibodies against fetal platelet antigens inherited from the father; it is still an underdiagnosed disease. This disease is considered the platelet counterpart of the RhD hemolytic disease of the fetus and newborn, yet in neonatal alloimmune thrombocytopenia the first child is affected with fetal and/or neonatal thrombocytopenia. There is a significant risk of intracranial hemorrhage and severe neurological impairment, with a tendency for earlier and more severe thrombocytopenia in subsequent pregnancies. This article reports a case of neonatal alloimmune thrombocytopenia in the second pregnancy affected and discusses diagnosis, management and the clinical importance of this disease.

Does the evaluation of coagulation factors contribute to etiological diagnosis of pleural effusions?

OBJECTIVE: The aim of this study was to identify the participation of the coagulation system in the differential diagnosis of pleural effusions. INTRODUCTION: Imbalance between immunologic and metabolic factors triggers a sequence of events resulting in pleural reactions and accumulation of fluid. The coagulation system, which is fundamental for the maintenance of homeostasis, contributes to the inflammatory process responsible for pleural effusions, and participates in cellular proliferation and migration as well as in the synthesis of inflammatory mediators. METHODS: We evaluated the laboratory profile of coagulation and fibrinolysis in 54 pleural fluids (15 transudates and 39 exudates). RESULTS: The coagulation system acts according to the pathophysiologic mechanisms involved in the development of pleural effusions. In inflammatory effusions (exudates), there is activation of coagulation with increased levels of fragment 1+2 and thrombin-antithrombin complex in addition to reduction of fibrinogen levels due to fibrinolysis and fibrin tissue incorporation. As a consequence, there is activation of the fibrinolytic system with increased levels of fibrin degradation products, including the D-dimer. These changes are not sufficient for differentiation of different subgroups of exudates. In transudates, these events were observed to a lesser degree. CONCLUSION: The coagulation system plays an important role in the development of pleural diseases. Coagulation tests show differences between transudates and exudates but not among exudate subgroups. Understanding the physiopathological mechanisms of pleural disorders may help to define new diagnostic and therapeutic approaches.

Successful management of neonatal alloimmune thrombocytopenia in the second pregnancy: a case report / Sucesso no manejo da trombocitopenia aloimune neonatal na segunda gestação: relato de caso

Neonatal alloimmune thrombocytopenia is a serious disease, in which the mother produces antibodies against fetal platelet antigens inherited from the father; it is still an underdiagnosed disease. This disease is considered the platelet counterpart of the RhD hemolytic disease of the fetus and newborn, yet in neonatal alloimmune thrombocytopenia the first child is affected with fetal and/or neonatal thrombocytopenia. There is a significant risk of intracranial hemorrhage and severe neurological impairment, with a tendency for earlier and more severe thrombocytopenia in subsequent pregnancies. This article reports a case of neonatal alloimmune thrombocytopenia in the second pregnancy affected and discusses diagnosis, management and the clinical importance of this disease.

A púrpura trombocitopênica neonatal aloimune é uma doença grave, na qual a mãe produz anticorpos contra antígenos plaquetários fetais herdados do pai, e é ainda subdiagnosticada na prática clínica. É considerada o equivalente plaquetário da doença hemolítica do recém-nascido, com a diferença que o primeiro filho é afetado, apresentando trombocitopenia fetal e/ou neonatal. Há risco significativo de hemorragia intracraniana e sequelas neurológicas graves, com tendência a trombocitopenia mais grave e mais precoce nas gestações subsequentes. Este artigo relata um caso de trombocitopenia aloimune neonatal na segunda gestação afetada e discute diagnóstico, manejo e importância clínica dessa doença na prática clínica.

Automonitorização e automanejo da anticoagulação oral / Oral anticoagulation self-monitoring and automanejoda

Esta revisão de 18 trabalhos mostrou que houve redução significante dos eventos trombóticos e da mortalidade com o emprego dos equipamentos portáteis. Embora tenha sido demonstrada diferença entre o autocontrole (quando o próprio paciente determinava a conduta terapêutica) e a automonitorização (quando o paciente somente quantificava o INR e transmitia o resultado para seu médico) quanto à redução de novos eventos tromboembólicos e sangramentos maiores, demonstrou-se melhora da qualidade de vida dos pacientes sob uso de dicumarínicos. Contudo, por vários motivos, essa auto avaliação não pode ser aplicada por todos os pacientes. Porém, sabe-se que existem vários aparelhos portáteis, com diferentes sensibilidades e custos diversos, e os autores não esclarecem quais os equipamentos usados e se foram observadas diferenças entre eles. De qualquer maneira, esta revisão mostra que o uso dos equipamentos portáteis é uma condição que pode alterar e melhorar a evolução clínica dos pacientes sob tratamento com drogas antagonistas da vitamina K e abre perspectivas para outros trabalhos avaliando diferenças de impacto econômico entre a avaliação tradicional e a realizada com aparelhos portáteis e também entre os diferentes aparelhos atualmente disponíveis no mercado.

Comparative study of platelet aggregation by turbidimetric and impedance methods in patients under acetylsalicylic acid antiplatelet therapy

INTRODUÇÃO: A hiperagregação (agregação excessiva) das plaquetas pode causar a formação de um trombo e a posterior oclusão dos vasos sanguíneos levando à isquemia. Esse fenômeno é responsável por doenças isquêmicas cardiovasculares, como angina pectoris e aterosclerose, bem como outras formas de isquemia, como o acidente vascular cerebral. Visando diminuir a função das plaquetas para reduzir a formação de trombos, o ácido acetilsalicílico vem sendo utilizado para tratamento antitrombótico, com diversos estudos mostrando sua eficácia. Dessa forma faz-se mister o uso de uma ferramenta laboratorial para o monitoramento da efetividade do tratamento, o que é feito por meio do teste de agregação plaquetária. O objetivo desse estudo foi comparar duas metodologias para esse exame (impedância elétrica e turbidimetria) em relação a trinta pacientes adultos de ambos os sexos em uso do fármaco. CONCLUSÃO: Os resultados mostraram uma boa correlação entre os métodos, possibilitando o uso concomitante de ambas as técnicas em laboratórios clínicos de rotina.

INTRODUCTION: Hyperaggregation of platelets can cause the formation of thrombi and subsequent occlusion of blood vessels leading to ischemia. This phenomenon can be responsible for ischemic cardiovascular diseases such as angina pectoris and atherosclerosis as well as other forms of ischemia such as stroke. To decrease platelet function and reduce the formation of thrombi, acetylsalicylic acid has been used for antithrombotic treatment, with several studies showing its effectiveness. Therefore it is necessary to use a laboratory tool to monitor the effectiveness of treatment, which is achieved through laboratory testing of platelet aggregation. The aim of this study was to compare two different methods (impedance and turbidimetry) to test platelet aggregation in 30 adult patients of both genders taking acetylsalicylic acid. CONCLUSION: The results show that there is a good correlation between these two methods and so both these techniques can be used in the clinical routine.

Ethnic differences in cerebral venous thrombosis.

BACKGROUND: Cerebral venous thromboses (CVT) with distinct clinical presentations have been shown worldwide. However, there is little information regarding race-ethnic differences in this disease. METHODS: We prospectively studied 50 CVT patients from Brazil, comparing clinical and laboratory data among white (W) and African-Brazilian (AB) patients. RESULTS: Seventy percent of the patients were female, 26 W and 23 AB, mean age 34.7 years. Multiple sinus CVT, deep CVT and worse outcome were significantly more frequent in AB than in W patients. There was a trend towards a higher frequency of factor V Leiden and prothrombin mutation in W than in AB, and of protein C deficiency in AB. CONCLUSIONS: CVT was more severe in AB patients than in W patients. Race-ethnic differences may account for the heterogeneous distribution of inherited thrombophilia in this series.

Hematological findings in Noonan syndrome.

OBJECTIVE: Noonan syndrome is a multiple congenital anomaly syndrome, and bleeding diathesis is considered part of the clinical findings. The purpose of this study was to determine the frequency of hemostatic abnormalities in a group of Noonan syndrome patients. METHOD: We studied 30 patients with clinical diagnosis of Noonan syndrome regarding their hemostatic status consisting of bleeding time, prothrombin time, activated partial thromboplastin time and thrombin time tests, a platelet count, and a quantitative determination of factor XI. RESULTS: An abnormal laboratory result was observed in 9 patients (30%). Although coagulation-factor deficiencies, especially factor XI deficiency, were the most common hematological findings, we also observed abnormalities of platelet count and function in our screening. CONCLUSIONS: Hemostatic abnormalities are found with some frequency in Noonan syndrome patients (30% in our sample). Therefore, we emphasize the importance of a more extensive hematological investigation in these patients, especially prior to an invasive procedure, which is required with some frequency in this disorder.