Clinical screening for menorrhagia and other bleeding symptoms in Nigerian women.

Objective: The objective of the study was to evaluate the prevalence of perceived bleeding symptoms in Nigerian women and the usefulness of a simple clinical screening tool for bleeding symptoms. Materials and Methods: A population-based cross-sectional survey of 1524 women of 16-50 years in Southeast Nigeria using a structured, prevalidated, pretested questionnaire was conducted. Results: A total of 1524 (85%) women responded with the mean age of 26 (10.6) years. Prevalence of bleeding symptoms was 24.6% and 11% of the women reported a positive family history of bleeding symptoms. There was a significant association between having a positive family history of bleeding disorder and experiencing bleeding symptoms (adjusted odds ratio: 0.12, 95% confidence interval: 0.06-0.22 P < 0.0001). Two hundred and six women experienced at least one bleeding symptom, 125 (8.2%) experienced at least two, whereas 43 (2.8%) experienced >3 bleeding symptoms. The most common perceived bleeding symptom was heavy menstrual bleeding (HMB) present in 83 women (22.2%), 141 (9.3%) reported a past history of HMB, 202 (13.3%) had heavy bleeds during most of their monthly cycle, and 351 (23%) requiring resuscitation with blood support. Conclusion: The prevalence of perceived bleeding symptoms among women is high, and HMB is the most common bleeding symptom. This clinical screening tool is easy and cost-effective in routinely identifying women with bleeding symptoms needing further hemostatic and obstetrics evaluation.

RésuméObjectif: L'objectif de l'étude était d'évaluer la prévalence des symptômes hémorragiques perçus chez les femmes nigérianes et l'utilité d'un outil de dépistage clinique simple des symptômes hémorragiques. Matériel et méthodes: enquête transversale auprès de la population auprès de 1 524 femmes de 16 à 50 ans dans le sud-est du Nigéria à l'aide d'un questionnaire structuré, prévalidé et prétesté. Résultats: Un total de 1524 (85%) les femmes ont répondu avec l'âge moyen de 26 (10,6) ans. La prévalence des symptômes hémorragiques était de 24,6% et 11% des femmes ont signalé un antécédents familiaux positifs de symptômes hémorragiques. Il y avait une association significative entre avoir des antécédents familiaux de saignement positifs trouble et présentant des symptômes hémorragiques (rapport de cotes ajusté: 0,12, intervalle de confiance à 95%: 0,06­0,22 P <0,0001). Deux cent et six femmes ont présenté au moins un symptôme de saignement, 125 (8,2%) en ont eu au moins deux, tandis que 43 (2,8%) ont eu> 3 saignements symptômes. Le symptôme de saignement perçu le plus courant était le saignement menstruel abondant (HMB) présent chez 83 femmes (22,2%), 141 (9,3%) ont signalé des antécédents de HMB, 202 (13,3%) ont eu des saignements abondants pendant la majeure partie de leur cycle mensuel et 351 (23%) ont dû être réanimés avec support sanguin. Conclusion: la prévalence des symptômes hémorragiques perçus chez les femmes est élevée et le HMB est le plus courant symptôme de saignement. Cet outil de dépistage clinique est simple et économique pour identifier systématiquement les femmes présentant des symptômes hémorragiques nécessitant évaluation hémostatique et obstétrique plus poussée.

Hemostatic Disorders: Physiology, Diagnostics, and Management.

A defect in any step of hemostasis can lead to potentially catastrophic results. The purpose of this article is to review hemostatic physiology, laboratory studies, and management of platelet and coagulation disorders to familiarize the advanced practice RN (APRN) with this often overlooked but critical system. Learning the underlying mechanisms allows for better understanding of the various disease states that can occur in the hematology and oncology settings.

Microfluidics in Haemostasis: A Review.

Haemostatic disorders are both complex and costly in relation to both their treatment and subsequent management. As leading causes of mortality worldwide, there is an ever-increasing drive to improve the diagnosis and prevention of haemostatic disorders. The field of microfluidic and Lab on a Chip (LOC) technologies is rapidly advancing and the important role of miniaturised diagnostics is becoming more evident in the healthcare system, with particular importance in near patient testing (NPT) and point of care (POC) settings. Microfluidic technologies present innovative solutions to diagnostic and clinical challenges which have the knock-on effect of improving health care and quality of life. In this review, both advanced microfluidic devices (R&D) and commercially available devices for the diagnosis and monitoring of haemostasis-related disorders and antithrombotic therapies, respectively, are discussed. Innovative design specifications, fabrication techniques, and modes of detection in addition to the materials used in developing micro-channels are reviewed in the context of application to the field of haemostasis.

Paediatric reference intervals for common coagulation assays in Chinese children as performed on the STA-R coagulation analyzer.

INTRODUCTION: In order to correctly manage the paediatric patients affected with haemostatic disorders, age-appropriate reference intervals should be used. The purpose of this study was to establish age-specific reference intervals for prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (aPTT) and fibrinogen (Fg). METHODS: In this study, a total of 34 234 apparently healthy children and adolescents aged 0-15 years were chosen as reference individuals. PT, TT, aPTT and Fg were performed on the STA-R coagulation analyzer. Outliers were eliminated using the Dixon D/R ratio rule. Partitioning by age was achieved using Harris and Boyd's standard normal deviate test. The lower (2.5th percentiles) and upper (97.5 percentiles) reference intervals were established using the nonparametric method. RESULTS: Compared with the adult group, the median time of PT was significantly different in the groups consisting of children aged 0-15 days, 15 days-1 month, 1-6 months and 11-15 years. The median time of APTT and TT was significantly prolonged in all paediatric age groups than in the adult group (P < .05). Compared with the adult group, the median values of Fg were significantly different in the groups consisting of children aged 0-15 days and 2-15 years. Our results showed that all coagulation assays required partitioning by age. CONCLUSION: Our results suggest that results of coagulation assays are highly dependent on age, and that age-specific reference intervals must be used to ensure proper evaluation of paediatric coagulation assays.

Primary Hemostatic Disorders and Late Major Bleeding After Transcatheter Aortic Valve Replacement.

BACKGROUND: Periprocedural and late (>30 days) bleedings represent major complications after transcatheter aortic valve replacement and have been identified as potential areas for improved patient care. OBJECTIVES: The authors sought to evaluate the impact of ongoing primary hemostasis disorders on late major/life-threatening bleeding complications (MLBCs). METHODS: Bleedings were assessed according to the VARC-2 (Valve Academic Research Consortium-2) criteria. Closure time of adenosine diphosphate (CT-ADP), a surrogate marker of high molecular weight von Willebrand multimers proteolysis was assessed 24 h after the procedure. Ongoing primary hemostasis disorder was defined by a CT-ADP >180 s. RESULTS: Among 372 patients who survived at 30 days, MLBCs occurred in 42 patients (11.3%) at a median follow-up of 383 days (interquartile range: 188 to 574 days). MLBCs were mainly of gastrointestinal origin (42.8%) and were associated with increased overall mortality (hazard ratio [HR]: 5.66; 95% confidence interval [CI]: 3.10 to 10.31; p < 0.001) and cardiac mortality (HR: 11.62; 95% CI: 4.59 to 29.37; p < 0.001). A 2.5-fold elevation of MLBCs could be evidenced in patients with a CT-ADP > 180 s (27.4% vs. 11.5%; p < 0.001). Multivariate regression analysis identified paravalvular leak (PVL) (HR: 6.31; 95% CI: 3.43 to 11.60; p < 0.0001) and CT-ADP > 180 s (HR: 3.08; 95% CI: 1.62 to 5.81; p = 0.0005) as predictor of MLBCs. CONCLUSIONS: MLBCs after transcatheter aortic valve replacement are frequent and associated with an increased morbidity and mortality. PVL and CT-ADP >180 s were identified as strong predictors for MLBCs. These findings strongly suggest that persistent HMW defects contribute to enhanced bleeding risk in patients with residual PVL.

[A hemostatic disorder caused by high shear stress: acquired von Willebrand syndrome].

The von Willebrand factors (VWFs) play critical role in hemostasis and thrombosis formation. VWFs are produced in and secreted as large multimers from endothelial cells, and shear stress-dependently cleaved into 2-80 multimers by their specific protease, ADATS13. Because high molecular weight VWFs play important roles in platelet aggregation, the loss of high molecular weight VWFs caused by pathological high-shear stress induces a hemostatic disorder known as acquired von Willebrand syndrome (AVWS) type IIA. The most well-known cause of this loss is aortic stenosis, which is accompanied by gastrointestinal bleeding most often as a result of angiodysplasia; this comprises a condition known as Heyde's syndrome. Additionally, various cardiovascular diseases that generate excessive high-shear stress in the blood stream, such as hypertrophic obstructive cardiomyopathy (HOCM), mitral regurgitation, pulmonary hypertension, and some congenital heart diseases, and mechanical circulatory support systems, such as left ventricular assist device (LVAD), cause AVWS.

Spectrum of hemostatic disorders in Indian females presenting with bleeding manifestations.

INTRODUCTION: Hemostatic disorders are often missed in women with bleeding particularly menorrhagia. Preexisting hemostatic disorders are now known as common risk factor for postpartum hemorrhage and prolonged bleeding in puerperium. Females with bleeding complaints constitute an important population referred to hematology clinic. Hence, we aim to evaluate the type and frequency of hemostatic disorders among females presenting with bleeding in a tertiary care hospital and a basic hemostatic laboratory. METHODS: Three-year data were retrospectively analyzed for 200 females with various bleeding complaints. Due to resource constraints, a hemostatic workup was done with prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen assay, clot solubility test, mixing studies, specific factor assays, platelet function test, and von Willebrand factor antigen level. RESULTS: A total of 200 females were investigated to identify the cause of their bleeding. Thirty-five of 200 (17.5%) females were found with an underlying bleeding disorder. Of these 35 females, 65.7% presented with bleeding from more than 1 site. Most common bleeding manifestation was spontaneous bruising in 18 of 35 (51.4%) patients followed by petechiae (48.6%). Inherited bleeding disorders were noted in majority. The most common inherited bleeding disorder identified was von Willebrand disease (VWD) in 34.3% females. Second most common disorder was Glanzmann's thrombasthenia accounting for 22.8%. Rare coagulation factor deficiency, such as factors VII, X, and XIII deficiencies, was noted. Three cases revealed acquired causes of coagulation defects. CONCLUSION: Underlying hemostatic defects should be searched for in women with unexplained bleeding complaints. This will not only help in diagnosis but also in proper management for future hemostatic challenges.

Recognition and Management of Hemostatic Disorders in Critically Ill Patients Needing to Undergo an Invasive Procedure.

Abnormal laboratory coagulation test results are frequently documented in critically ill patients, and these patients often also need to undergo invasive procedures. Clinicians have an understandable desire to minimize any perceived heightened risk of bleeding complications in those patients who require invasive procedures. In this setting, prophylactic administration of platelets or plasma is commonplace. This review explores the nature of these sequential statements and the degree to which these statements are supported by evidence. We discuss the complexity of managing the low risk of procedure-related bleeding in a setting where coagulation tests fail to reliably predict this risk. The role of prophylactic transfusion of platelets and plasma and correction of medication-induced coagulopathy is also reviewed. New strategies are required to improve the evidence base, including novel methodological approaches or the use of a clinical scoring system.

Establishing reference intervals in the coagulation laboratory.

INTRODUCTION: Obtaining a reference interval (RI) is a challenge for any laboratory and becomes more complicated in the coagulation laboratory due to testing on samples with limited stability on reagents that are poorly standardized. Reference intervals are required to be able to evaluate results in relation to a patients' hemostatic disorder. This becomes one of the most important tasks conducted in the coagulation laboratory. However, many laboratories lack the time, finances and in many cases the expertise to conduct this study. METHODS: Many RI are obtained from package inserts, or from publications written by experts in lieu of laboratories conducting their own studies. An overview of validating reference intervals and options for verifying or transference of reference intervals is discussed. RESULTS: Based on the confidence interval and the acceptability of risk laboratories are willing to accept, coagulation laboratories have options to conduct robust studies for their RI. Data mining or global reference studies may help to provide data for age specific ranges. CONCLUSIONS: Pre-analytical variables and selection of healthy subjects have the largest impact on coagulation testing outcomes and need to be well controlled during the establishment of reference intervals. Laboratories have options in lieu of conducting a full validation on how to verify RI based on smaller RI studies or transference of RI after determining compatibility of the original RI study.

Hemostatic Disorders Associated with Hepatobiliary Disease.

The liver plays a crucial role in all aspects of coagulation because most factors that regulate procoagulation, anticoagulation, and fibrinolysis are produced, cleared, and/or activated in the liver. Establishing the coagulation status of an individual patient with hepatobiliary disease can therefore be challenging. Although, classically, patients with hepatobiliary disease were thought of as potentially hypocoagulable, hypercoagulability also occurs. The article summarizes the breadth of coagulation abnormalities that have been reported in dogs and cats with hepatobiliary disease and provides strategies to respond to bleeding and thrombotic risk.

Neonatal Hemostatic Disorders: Issues and Challenges.

Neonates form a unique cohort with distinct features associated with the hemostatic system compared with older children and adults. The development of the human hemostatic system begins around 10 weeks in utero and continues to evolve during childhood. This dynamic period termed developmental hemostasis should be taken into consideration when diagnosing a neonate with disorders of bleeding or thrombosis.

Preoperative hemostatic assessment: a new and simple bleeding questionnaire.

PURPOSE: Current recommendations for the assessment of the risk of perioperative bleeding limit coagulation testing to patients with a personal and/or family history of bleeding. As no simple preoperative screening questionnaire is currently available, we assessed the performance of a novel screening questionnaire for its ability to detect bleeding disorders. METHODS: A dichotomized, seven-point questionnaire named HEMSTOP (Hematoma, hEmorrhage, Menorrhagia, Surgery, Tooth extraction, Obstetrics, Parents) was applied to three groups of subjects: patients referred to hemostasis specialists for bleeding symptoms for whom any kind of perioperative hemostatic precautions were subsequently recommended (n = 38); patients referred to hemostasis specialists for whom precautions were not required (n = 75); healthy volunteers (n = 70). We calculated the sensitivity and specificity of HEMSTOP scores and compared them with the discriminative performances of standard blood coagulation assays (prothrombin time, activated partial thromboplastin time). RESULTS: Patients requiring perioperative hemostatic precautions had greater median [interquartile range] HEMSTOP scores (2 [2-3]) than patients not requiring precautions (1 [1-2]) and healthy controls (0 [0-0]); P < 0.001. A HEMSTOP score ≥ 2 had a specificity of 98.6% [95% confidence interval (CI), 92.3 to 100] and a sensitivity of 89.5% (95% CI, 75.2 to 97.1). The 26.3% (95% CI, 13.4 to 43.1) sensitivity of the standard coagulation times was much lower. CONCLUSION: The HEMSTOP score discriminates patients at an elevated risk for bleeding with recommended perioperative precautions from those without such recommendations as well as from healthy participants. Further evaluation of the HEMSTOP score is required for a better evaluation of its definitive usefulness to predict the risk of perioperative bleeding.

Our experience with pre-operative haemostatic assessment of paediatric patients undergoing adenotonsillectomy at Federal Medical Centre, Makurdi.

BACKGROUND: In 2-4% of all patients requiring adenoidectomy, tonsillectomy or adenotonsillectomy, pre-operative screening tests for coagulation disorders are indicated to detect surgical bleeding complications. However, because of cost effect on the patients, the usefulness of these tests is being challenged. We therefore highlight our experience in paediatric patients undergoing adenoidectomy, tonsillectomy or both in our centre. PATIENTS AND METHODS: This is a 3½-year analysis of the data of 165 paediatric patients who had adenoidectomy, tonsillectomy or both over the study period. The data collected included age, sex, procedure done and detailed clinical bleeding history. RESULTS: A total of 165 children had either adenoidectomy or tonsillectomy, or both. There were 76 males and 89 females giving a male to female ratio of 1:1.2. Their ages ranged from 10 months to 18 years. Eighty-five (51.5%) patients had adenotonsillectomy, 48 (29.1%) and 32 (19.4%) had only tonsillectomies and adenoidectomies, respectively. Only 11 (6.7%) families volunteered the history of either prolonged bleeding with minor injury on the skin or occasional slight nose bleeding. Six (3.6%) patients including 3 of the children with positive family history had posttonsillectomy bleed, out of which 4 (66.7%) were moderate whereas the remaining 2 (33.3%) were severe bleeding, which was not statistically significant (P = 0.041). The two cases of severe bleeding had fresh whole blood transfused whereas the rest that had no bleeding issues were discharged home 48 h postoperatively. CONCLUSION: Our experience in this study suggests that detailed bleeding history is necessary as well as pre-operative haemostatic assessment, if available and affordable for paediatric patients undergoing adenotonsillectomy.

[Haemostatic disorders in children]. / Hämostaseologie in der Pädiatrie.

Haemorrhagic and thrombotic events occur in both children and adults. The underlying causes are congenital or acquired disorders. In contrast to haemorrhagic disorders, inherited thrombotic disorders nearly exclusively in association with additional external risk factors lead to thrombotic events predominantly during the newborn period and adolescence. It is necessary to be aware of age-specific properties of coagulation in order to correctly interpret clinical and laboratory findings and to provide optimal care for children with haemorrhagic and thrombotic complications.

Neonatal haemostasis. Impact on bleeding and thrombosis.

The maturation and postnatal development of the human coagulation system results in significant and important differences in the coagulation and fibrinolysis of neonates and young children compared to older children and adults. Importantly, these differences, which mostly reflect the immaturity of the neonatal haemostasis system, are functionally balanced. Healthy neonates show no signs of easy bruising or other bleeding diathesis and no increased tendency to thrombosis for any given stimulus compared to adults. Systemic diseases may affect haemostasis, thus predisposing ill neonates to increased risk for haemorrhagic or thrombotic complications. In hospitalized children, neonates have increased risk of developing thrombosis compared to infants and children, mostly associated with the presence of central venous catheter. For diagnosis of haemostasis disorders, diagnostic laboratories processing pediatric samples should use age, analyzer and reagent appropriate reference ranges. Age specific guidelines should be followed for the management of neonates with hemostatic disorders.

Effects of transcutaneous aortic valve implantation on aortic valve disease-related hemostatic disorders involving von Willebrand factor.

BACKGROUND: Aortic valve stenosis (AVS) can be complicated by bleeding associated with acquired type 2A von Willebrand syndrome. The association of AVS and gastrointestinal bleeding from angiodysplasia is defined as Heyde syndrome. We sought to evaluate the effect of transcutaneous aortic valve implantation (TAVI) on hemostasis disorders and to assess its effectiveness to treat Heyde syndrome. METHODS: We prospectively enrolled 49 consecutive patients with severe AVS addressed for TAVI at our institution. Biological hemostasis parameters involving von Willebrand factor (vWF) were assessed at baseline and 1 week after the procedure. RESULTS: At baseline, a significant link between vWF abnormalities and the severity of AVS was evidenced: mean aortic transvalvular gradient was negatively correlated with the levels of vWF antigen (vWF:Ag) (r = -0.29; P < 0.05), vWF ristocetin cofactor activity (r = -0.402; P = 0.006), and vWF collagen-binding activity (vWF:CB; r = -0.441; P = 0.005). One week after the procedure, a significant increase of vWF:Ag, vWF ristocetin cofactor activity, and vWF:CB was evidenced in the whole cohort (respectively, 3.32 vs. 2.29 IU/mL, P < 0.001; 2.98 vs. 1.86 IU/mL, P < 0.001; and 3.16 vs. 2.16 IU/mL, P < 0.001). Patients with pre-TAVI vWF abnormalities consistent with a type 2A vWF syndrome (ratio vWF:CB/vWF:Ag < 0.7) preferentially improved their vWF function with respect to patients with a normal ratio (relative increase of vWF:CB of 63.8% vs. 3.5%). CONCLUSIONS: Hemostasis parameters involving vWF are improved after TAVI, especially in patients with pre-existing abnormalities consistent with acquired type 2A von Willebrand syndrome.

Hemostatic abnormalities in young females with heavy menstrual bleeding.

OBJECTIVE: To study the prevalence of hemostatic abnormalities, including bleeding disorders and risk factors, in young females referred to a multidisciplinary clinic for evaluation of heavy menstrual bleeding (HMB). METHODS: Retrospective chart review was undertaken for 131 post-menarchal girls with HMB, 7 to 17 years of age, enrolled in the institutional 'Menorrhagia Data Registry' protocol. The diagnostic approach included: (1) complete blood count, prothrombin time, partial thromboplastin time, fibrinogen, von Willebrand panel (2) platelet aggregometry, specific clotting factor assay, fibrinolytic pathway analysis, and factor XIII level as needed. The prevalence of hemostatic abnormalities and the prognostic significance of clinical variables associated with hemostatic abnormalities in young girls with HMB were evaluated. RESULTS: A hemostatic abnormality was identified in 69 (53%) young girls with HMB. Of these, 27 (21%) had an underlying bleeding disorder and 42 (32%) had a risk factor for bleeding, namely low von Willebrand factor activity. A larger number of girls with underlying bleeding disorder had personal history of other bleeding symptoms (48% vs 31%) and bleeding after surgical or dental procedure (25% vs 8%) when compared to females without hemostatic abnormality. Furthermore, girls with risk factor for bleeding (low vWF activity) were more likely to have bleeding after surgical or dental procedure (15% vs 8%) and family history of bleeding (79% vs 60%) than patients without hemostatic abnormality. CONCLUSIONS: There is high prevalence of hemostatic abnormalities, including bleeding disorders and risk factors, in young girls with HMB. These findings support comprehensive and systematic hemostatic evaluation in this group of patients.