Bleeding Disorders In Patients Research Articles

Thromboelastogram and coagulation function index: relevance for female breast cancer.

Screening and postoperative intervention of breast tumors are critical for the effective diagnosis and treatment of disease development, and reliable diagnostic/screening methods become a key link. Thromboelastogram (TEG), routine platelet (PLT) count, and the coagulation function indicators in patients with different breast diseases were determined and analyzed to explore their predictive value in secondary bleeding disorders. A total of 131 patients with breast diseases, admitted to Jiangsu University Affiliated Hospital from January 2019 to December 2022, were selected as the research subjects. The detection items were analyzed using the receiver operating curve (ROC) after grouping for secondary bleeding disorders of patients with breast cancer. The reaction (R) and the coagulation (K) times were lower in the malignant breast disease group, while the coagulation angle (α), maximum amplitude (MA), coagulation index (CI), fibrinogen (FIB), and D-dimer (D-D) were higher than those in the benign breast disease group. The t-tests proved that the MA and FIB values were statistically significant (p < 0.05) in the benign and malignant breast disease groups. The R and K in patients with breast diseases were positively correlated with the activated partial thromboplastin time (aPTT) and D-D, but were negatively correlated with PLT. The α angle was negatively correlated with aPTT and D-D, but was positively correlated with PLT. The MA for PLT function was positively correlated with FIB and PLT. CI was negatively correlated with aPTT, thrombin time (TT), and D-D, but was positively correlated with PLT. ROC curve analysis showed that the CI and α angle had a significant predictive value, whereas the correlation of the other indicators was relatively low. Coagulation tests showed significant differences in patients with breast cancer, differing from those with benign breast diseases. TEG combined with conventional coagulation indicators is potentially valuable for the prediction of secondary bleeding disorders in patients with breast cancer.

Assessment of Bleeding Risks and Patient Knowledge Levels About Bleeding Disorders in Patients Referred to the Oral and Maxillofacial Surgery Clinic

Assessment of Bleeding Risks and Patient Knowledge Levels About Bleeding Disorders in Patients Referred to the Oral and Maxillofacial Surgery Clinic

PB1370 Thrombocytosis and Acquired Bleeding Disorders in Patients with Myeloproliferative Neoplasms

PB1370 Thrombocytosis and Acquired Bleeding Disorders in Patients with Myeloproliferative Neoplasms

Management of antithrombotic treatment and bleeding disorders in patients requiring venous access devices: A systematic review and a GAVeCeLT consensus statement.

Insertion of venous access devices (VAD) is usually considered a procedure with low risk of bleeding. Nonetheless, insertion of some devices is invasive enough to be associated with bleeding, especially in patients with previous coagulopathy or in treatment with antithrombotic drugs for cardiovascular disease. The current practices of platelet/plasma transfusion in coagulopathic patients and of temporary suspension of the antithrombotic treatment before VAD insertion are based on local policies and are often inadequately supported by evidence, since many of the clinical studies on this topic are not recent and are not of high quality. Furthermore, the protocols of antithrombotic treatment have changed during the last decade, after the introduction of new oral anticoagulant drugs. Though some guidelines address some of these issues in relation with specific procedures (port insertion, etc.), no evidence-based document covering all the aspects of this clinical problem is currently available. Thus, the Italian Group of Venous Access Devices (GAVeCeLT) has decided to develop a consensus on the management of antithrombotic treatment and bleeding disorders in patients requiring VADs. After a systematic review of the available evidence, the panel of the consensus (which included vascular access specialists, surgeons, intensivists, anesthetists, cardiologists, vascular medicine experts, nephrologists, infective disease specialists, and thrombotic disease specialists) has structured the final recommendations as detailed answers to three sets of questions: (1) which is an appropriate classification of VAD-related procedures based on the specific bleeding risk? (2) Which is the appropriate management of the patient with bleeding disorders candidate to VAD insertion/removal? (3) Which is the appropriate management of the patient on antithrombotic treatment candidate to VAD insertion/removal? Only statements reaching a complete agreement were included in the final recommendations, and all recommendations were offered in a clear and synthetic list, so to be easily translated into clinical practice.

RASopathies and hemostatic abnormalities: key role of platelet dysfunction

BackgroundBleeding anomalies have been reported in patients affected by Noonan syndrome. No study has been performed in patients with molecularly confirmed RASopathy. We aimed to characterize the frequency and types of bleeding disorders in patients with RASopathies and evaluate any significant association with laboratory findings.Patients and methodsForty-nine individuals (PTPN11, n = 27; SOS1, n = 7; RIT1, n = 3; SPRED1, n = 1; LZTR1, N = 3; RAF1, n = 2; BRAF, n = 4; MEK1, n = 1; MEK2, n = 1), and 49 age- and sex-matched controls were enrolled. The “Paediatric Bleeding Questionnaire Scoring Key” was administered to patients and families. Laboratory screening tests including clotting factors dosing, platelet count, Prothrombin Time and Partial Thromboplastin Time, were employed both in patients and controls to characterize the bleeding diathesis. A subgroup of 29/49 patients and 29/49 controls was also tested for platelet function.ResultsRegardless of the gene involved, pathological paediatric bleeding scores were recorded in 14/49 (28.5%) patients. Indeed, 7 were mutated in PTPN11, 3 in SOS1, 2 in RIT1, 1 in BRAF, and 1 in MEK1. Compared to patients with normal bleeding scores, those with pathologic bleeding score showed higher prevalence of splenomegaly (p = 0.006), prolonged aPTT (p = 0.04), lower levels of coagulation factor V (FV, p = 0.001), FVII (p = 0.003), FX (p = 0.0008) and FXIII (p = 0.002), higher vWAg (p = 0.04), and lower platelet sensitivity to Ristocetin (p = 0.001), arachidonic acid (AA) (p = 0.009) and collagen (p = 0.01). The presence of hematomas inversely correlated with factor V (p = 0.002), factor VII (p = 0.003), factor X (p = 0.002) and factor XIII (p = 0.004) levels, and directly correlated with platelet response to collagen (p = 0.02) and AA (p = 0.01). The presence of splenomegaly directly correlated with the presence of hematoma (p = 0.006), platelet response to Ristocetin (p = 0.04) and AA (p = 0.04), and inversely correlated with factor V levels (p = 0.03).ConclusionsPatients with RASopathies and a bleeding tendency exhibit multiple laboratory abnormalities, including platelet-related disorders. Splenomegaly is frequently detected and might be a suggestive sign for qualitative platelet dysfunction. A comprehensive clinical assessment should be carried out at diagnosis, during the follow-up and before any surgical procedures. Since there is currently no consensus on management of bleeding complications, it is important that physicians closely monitor these patients.

Optimization of anti-ADAMTS13 antibodies for the treatment of ADAMTS13-related bleeding disorder in patients receiving circulatory assist device support

ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type-1 motif 13)-related bleeding disorder has been frequently observed as a life-threatening clinical complication in patients carrying a circulatory assist device. Currently, treatment modalities for the bleeding disorder are very limited and not always successful. To address the unmet medical need, we constructed humanized antibodies of mouse anti-ADAMTS13 antibody A10 (mA10) by using complementarity-determining region (CDR) grafting techniques with human antibody frameworks, 8A7 and 16E8. The characteristics of the two humanized A10 antibodies, namely A10/8A7 and A10/16E8, were assessed in vitro and in silico. Among the two humanized A10 antibodies, the binding affinity of A10/16E8 to ADAMTS13 was comparable to that of mA10 and human-mouse chimeric A10. In addition, A10/16E8 largely inhibited the ADAMTS13 activity in vitro. The results indicated that A10/16E8 retained the binding affinity and inhibitory activity of mA10. To compare the antibody structures, we performed antibody structure modeling and structural similarity analysis in silico. As a result, A10/16E8 showed higher structural similarity to mA10, compared with A10/8A7, suggesting that A10/16E8 retains a native structure of mA10 as well as its antigen binding affinity and activity. A10/16E8 has great potential as a therapeutic agent for ADAMTS13-related bleeding disorder.

Do we need to evaluate patients with spontaneous subconjunctival haemorrhage for bleeding disorders?

Subconjunctival haemorrage (SCH) is a frequent bleeding manifestation and a common cause of visits to the primary care. Trauma in young patients and vascular damage such as hypertension in the elderly are the most common causes of SCH and the prevalence of haematological diseases is <1%. We aimed to evaluate the prevalence of congenital or acquired bleeding disorders in patients with once or recurrent SCH. It is a retrospective study and included fifty-two patients with SCH whose aetiologic factor was not detected. Haemostatic tests were studied in 52 patients (25 male and 27 females). All patients included were evaluated for congenital or acquired bleeding disorder and SCH with once and those with two or more were compared for the laboratory results. Type I von Willebrand disease (vWD) was diagnosed in one patient with recurrent SCH and one patient with single SCH (3.8%). The prevalence of patients with type 1 vWD in the study was not statistically significant when compared with the frequency of vWD in the normal population. Fibrinogen level was found to be statistically higher in patients who had SCH once than those who had recurrent SCH. However, fibrinogen level was in normal range in all patients. There was no increase in the incidence of congenital or acquired bleeding disorder in SCH compared with normal population. Fort this reason, it was thought there was no need for evaluation for bleeding disorders in spontaneous SCH.

Methods of preserving platelets: cryopreservation as a reasonable option for its implementation in Argentina

Platelets are one of the most widely used blood components in transfusion medicine, given their importance in the prevention of bleeding disorders in patients with multifactorial thrombocytopenia and Asian non-immunological etiology, as well as in the management of traumatic or blood-related surgical treatments. Given its extensive use and the constant demand for it to be used within the different procedures associated with medicine, it is the objective of both hemotherapy services and blood banks to ensure that blood product components are constantly available to meet such requirements. The main challenge with this resource is its short useful life (5–7 days) which limits its availability, especially in the Latin American context where the production of blood components as well as the resources allocated for this purpose by state entities to blood banks, are generally limited. Cryopreservation at –80°C using dimethylsulfoxide as a preservative solution is a technique used since the 1950s to prolong platelet survival, the improvement of which has been remarkable in recent years, thereby constituting an alternative solution to this problem.

MicroRNA Prediction in the FVIII Gene Locus: A Step Towards Hemophilia A Control

Background: Various mutations in factor VIII (F8) gene locus are led to an X-linked bleeding disorder in patients with hemophilia A. One of the leading causes of inefficient treatment available for hemophilia A is the lack of specific and sensitive diagnostic procedure for the disease. The discovery of a functional role of microRNAs (miRNAs) in the pathogenesis of a wide range of human diseases makes them the potential, non-invasive, biomarker candidates for hemophilia A. Therefore, advances in computational tools for miRNA discovery leads to numerous recent publications on miRNAs as putative biomarkers. Objectives: The current study aimed at scanning the F8 gene region to predict novel miRNAs as regulators of the F8 gene. Methods: The potential of the FVIII locus to express new miRNAs was studied via reliable bioinformatics databases, such as SSCprofiler, RNAfold, miREval, miR-Find, FOMmiR, UCSC genome browser, and miRBase. Results: Data analysis from previously mentioned databases offered two stem-loop structures predicted to express novel miRNAs. Conclusions: The presented stem-loop structures can be used as powerful non-invasive biomarkers in early diagnosis of the disease and regulation of the factor VIII gene after subsequent experimental verification.

The Noonan Syndrome Gene Lztr1 Controls Cardiovascular Function by Regulating Vesicular Trafficking.

Noonan syndrome (NS) is one of the most frequent genetic disorders. Bleeding problems are among the most common, yet poorly defined complications associated with NS. A lack of consensus on the management of bleeding complications in patients with NS indicates an urgent need for new therapeutic approaches. Bleeding disorders have recently been described in patients with NS harboring mutations of LZTR1 (leucine zipper-like transcription regulator 1), an adaptor for CUL3 (CULLIN3) ubiquitin ligase complex. Here, we assessed the pathobiology of LZTR1-mediated bleeding disorders. Whole-body and vascular specific knockout of Lztr1 results in perinatal lethality due to cardiovascular dysfunction. Lztr1 deletion in blood vessels of adult mice leads to abnormal vascular leakage. We found that defective adherent and tight junctions in Lztr1-depleted endothelial cells are caused by dysregulation of vesicular trafficking. LZTR1 affects the dynamics of fusion and fission of recycling endosomes by controlling ubiquitination of the ESCRT-III (endosomal sorting complex required for transport III) component CHMP1B (charged multivesicular protein 1B), whereas NS-associated LZTR1 mutations diminish CHMP1B ubiquitination. LZTR1-mediated dysregulation of CHMP1B ubiquitination triggers endosomal accumulation and subsequent activation of VEGFR2 (vascular endothelial growth factor receptor 2) and decreases blood levels of soluble VEGFR2 in Lztr1 haploinsufficient mice. Inhibition of VEGFR2 activity by cediranib rescues vascular abnormalities observed in Lztr1 knockout mice Conclusions: Lztr1 deletion phenotypically overlaps with bleeding diathesis observed in patients with NS. ELISA screening of soluble VEGFR2 in the blood of LZTR1-mutated patients with NS may predict both the severity of NS phenotypes and potential responders to anti-VEGF therapy. VEGFR inhibitors could be beneficial for the treatment of bleeding disorders in patients with NS.

The Evaluation of Hematologic Screening and Perioperative Management in Patients with Noonan Syndrome: A Retrospective Chart Review

To assess the potential impact of using screening recommendations for bleeding disorders in patients with Noonan syndrome on perioperative bleeding complications. We performed a retrospective, single-site cohort study; patients were identified by query of the electronic medical record. All patients with a clinical diagnosis of Noonan syndrome over a 10-year period were included. Data on surgeries, hematologic evaluation, bleeding symptoms, and bleeding complications were extracted. Surgeries were graded as major or minor. We identified 101 patients with Noonan syndrome, 70 of whom required surgery for a total of 164 procedures. Nine patients (9/70; 12.8%) had bleeding complications, occurring in those without comprehensive testing or perioperative intervention and undergoing major or dental surgery. Based on these findings, the risk of a bleeding complication for patients with Noonan syndrome who did not have comprehensive testing or perioperative intervention was 6.2% (95% CI 2.3%-10.1%), indicating the number needed to treat or screen would be 16 to prevent 1 bleeding complication (95% CI 9.9-43.9). The majority of patients had either no or incomplete evaluation (59 of 101; 58.4%). With proper evaluation and management, the bleeding risk in patients with Noonan syndrome can be minimized. Efforts are needed to address the knowledge and implementation gap in this evaluation.

Spectrum of Bleeding Disorders In Pakistan: A Cross-Sectional Study

Abstract This is a cross-sectional study conducted to determine the frequency and spectrum of bleeding disorders in different regions of Pakistan and to improve facilities to cure them. Samples were collected from different regions of Pakistan. There bleeding presentation and history of the family were recorded. 435 patients were selected from the different regions of Pakistan; 318 male (73%) and 117 female (26%). Laboratory analysis included Prothrombin time, Activated partial thromboplastin time, Bleeding time, platelet counts and fibrinogen assay were performed. According to their results, vWF:Ag, vWF:RCo, inhibitor screening, Bethesda test, urea clot solubility test, and platelet aggregation test were performed to diagnosed bleeding disorders in patients. Out of 435 patients, 283 constitute CBD, 80 diagnosed with RBD, and 72 remain undiagnosed. Patients diagnosed with 52% hemophilia A, 1.4% with its inhibitor, 8.4% with hemophilia B, 0.35% with its inhibitor, 3.88% with VWD, 33.5%with its type III. A rare bleeding disorder is diagnosed in 80 subjects with 20% fibrinogen, 16.25% FXIII, 15% FVII, 11.25% FV, 10% vitamin k dependent factors, 8.25% GT, 5% FXII and epinephrine, 2.5% FII and FX and 1.25% FV + FVIII, BSS and FXI deficiencies. Clinical bleeding episodes varied in patients with respect to its deficiencies include gum bleeding, menorrhagia, hematoma, bruises, umbilical cord bleeding, hemorrhagia, and hemarthrosis. Study shows that hemophilia A is more frequent than hemophilia B. vWD type III has a higher prevalence. In RBD, fibrinogen deficiency is the most common, followed by FXIII, FVII, and FV respectively.

Combination of acquired von Willebrand syndrome (AVWS) and Glanzmann thrombasthenia in monoclonal gammopathy of uncertain significance (MGUS), a case report

BackgroundAutoimmune paraphenomena, are associated with B-cell lymphoproliferative disorders, including monoclonal gammopathy of uncertain significance. These paraphenomena can rarely include acquired bleeding disorders.Case presentationThis case study reports an unusual clinical presentation of 2 acquired bleeding disorders, Acquired von Willebrand syndrome (disease) and Acquired Glanzmann’s thrombasthenia, in an elderly patient with monoclonal gammopathy of uncertain significance.ConclusionsAcquired bleeding disorders are often underdiagnosed and a high degree of clinical suspicion is required. The patient in this study demonstrated platelet aggregometry which was atypical for isolated Glanzmann’s thrombosthenia because of the severe concomitant endogenous decrease in von Willebrand factor. There was an absence of platelet aggregation to all tested agonists including ristocetin. Once the diagnosis was made, however, the patient showed a partial response to intravenous immunoglobulin confirming the immunological pathogenesis in this case. This case highlights the need to consider acquired bleeding disorders in patients with a possible predisposing factor.

Evaluation of bleeding disorders in patients with Noonan syndrome: a systematic review.

BackgroundNoonan syndrome (NS) is an autosomal dominant genetic condition that has a number of clinical features, including bleeding diathesis and a number of hematological abnormalities including clotting factor deficiencies, von Willebrand disease and abnormal platelet count/function.MethodsWe evaluated the frequency/types of bleeding disorders, and associated hematological laboratory findings, in patients with NS, using published data from 1965 to 2014.ResultsOf 45 studies identified, 31 included data for 428 patients with NS. Of these patients, 43% had reported bleeding, 26% had no reported bleeding and no bleed data was reported for 31%. Most patients (90%) had bleeding-related laboratory test abnormalities, but only 194 (45%) had a confirmed diagnosis of a specific bleeding disorder. Abnormal laboratory tests included: prolonged prothrombin time, activated partial thromboplastin time, and other platelet-related disorders. Of the 194 patients with a confirmed diagnosis of a specific bleeding disorder, 153 (79%) had single clotting factor deficiencies, von Willebrand disease or platelet-related disorders, and 41 (21%) had multiple deficiencies including platelet-related disorders.ConclusionAs patients with NS can experience multiple bleeding disorders, including abnormal platelet function, clinical evaluations should be performed at diagnosis, after diagnosis, before any surgery is undertaken, and if patients become symptomatic.

Patient with thrombophilia on anticoagulation with recurrent bleeding

Acquired haemophilia A is a rare life threatening bleeding disorder often presenting in older individuals with autoimmune disorders and malignancy, and postpartum state. This case study reports a patient on stable warfarin therapy for 10 years for an unprovoked above knee deep vein thrombosis with a known inherited homozygous factor V Leiden mutation. She had increasing bleeding thought to be warfarin related despite a therapeutic INR. Her coagulation profile was markedly abnormal with a disproportionately prolonged aPTT leading to further investigations confirming presence of an acquired factor VIII inhibitor. The patient was treated with high doses of steroids and rituximab. This case highlights the diagnostic pitfalls of a bleeding disorder in patients on warfarin therapy. The co-existence of acquired factor VIII inhibitor with homozygous factor V Leiden mutation poses unique treatment challenges.

Self-Nanoemulsifying Lyophilized Tablets for Flash Oral Transmucosal Delivery of Vitamin K: Development and Clinical Evaluation

Owing to limited solubility, vitamin K undergoes low bioavailability with large inter-individual variability after oral administration. This article aimed to prepare self-nanoemulsifying lyophilized tablets (SNELTs) for the flash oral transmucosal delivery of vitamin K. Twenty-one formulae of vitamin K self-nanoemulsifying drug delivery systems (SNEDDS) were prepared using different concentrations of vitamin K, Labrasol, and Transcutol according to mixture design. The SNEDDS was loaded on porous carriers and formulated as lyophilized tablets. The release profile and the pharmacokinetic parameters of vitamin K SNELTs were evaluated in comparison with commercial tablets and ampoules on human volunteers. Results revealed that the optimized SNEDDS showed the smallest and most stable nanoemulsion globules. SNELTs were prepared successfully and showed substantial superiority drug release compared with the commercial tablets. Interestingly, SNELTs enhanced both rate and extent of vitamin K absorption as well as relative bioavailability (169.67%) in healthy subjects compared with the commercial tablets. SNELTs revealed promising no significant difference in the area under the curve compared with the commercial intramuscular injection. SNELTs enhanced dissolution and bioavailability that expected to have the strong impact on the efficiency of vitamin K in the prophylaxis and treatment of bleeding disorders in patients with hepatic dysfunction.

Paradoxical Effect of Nonphysiological Shear Stress on Platelets and von Willebrand Factor.

Blood can become hypercoagulable by shear-induced platelet activation and generation of microparticles. It has been reported that nonphysiological shear stress (NPSS) could induce shedding of platelet receptor glycoprotein (GP) Ibα, which may result in an opposite effect to hemostasis. The aim of this study was to investigate the influence of the NPSS on platelets and von Willebrand factor (vWF). Human blood was exposed to two levels of NPSS (25 Pa, 125 Pa) with an exposure time of 0.5 s, generated by using a novel blood-shearing device. Platelet activation (P-selectin expression, GPIIb/IIIa activation and generation of microparticles) and shedding of three platelet receptors (GPIbα, GPVI, GPIIb/IIIa) in sheared blood were quantified using flow cytometry. Aggregation capacity of sheared blood induced by ristocetin and collagen was evaluated using an aggregometer. Shear-induced vWF damage was characterized with Western blotting. Consistent with the published data, the NPSS caused significantly more platelets to become activated with increasing NPSS level. Meanwhile, the NPSS induced the shedding of platelet receptors. The loss of the platelet receptors increased with increasing NPSS level. The aggregation capacity of sheared blood induced by ristocetin and collagen decreased. There was a loss of high molecular weight multimers (HMWMs) of vWF in sheared blood. These results suggest that the NPSS induced a paradoxical effect. More activated platelets increase the risk of thrombosis, while the reduction in platelet receptors and the loss of HMWM-vWF increased the propensity of bleeding. The finding might provide a new perspective to understand thrombosis and acquired bleeding disorder in patients supported with blood contacting medical devices.

Abstract 599: Lighting Up P2Y12 Oligomers: Insights into the Role of Oligomerization in P2Y12 Function

Introduction: Little is known about the role of P2Y12 oligomerization in receptor function and whether P2Y12 receptor mutations associated with human bleeding disorders may be explained by alterations in oligomerization. Objectives: 1) To determine whether P2Y12 homo- and hetero-oligomers are constitutive or dynamically regulated. 2) To explore whether P2Y12 mutants R256Q and R265W (previously detected in patients with abnormal bleeding, but with unaltered ADP binding) have different oligomerization affinities or kinetics and determine whether differences in P2Y12 oligomerization explain the functional defects. Methods: We employed a Venus-based Bimolecular Fluorescence Complementation (BiFC) approach in HEK293T cells transiently co-expressing P2Y12 or its mutant forms (R256Q or R265W) tagged with either the N-terminal (P2Y12-VN) or C terminal fragment (P2Y12-VC) of Venus, to characterize their homomeric interactions, in live cells using confocal microscopy and quantitative flow cytometry assays. Results: Agonist-independent formation of P2Y12 receptor homo-oligomers were detected on cell membranes. Time lapse imaging showed movement of P2Y12 receptor pairs from the endoplamic reticulum and Golgi network to the plasma membrane, suggesting that they are constitutive and required for export. Co-expression of P2Y12-VN with increasing amounts of P2Y12-VC demonstrated a dose-dependent increase in the fluorescence intensity of Venus, and reached saturation at a ratio of 1:3. Interestingly, the fluorescence intensities of homomeric P2Y12-R256Q-VN and R256Q-VC and, separately, P2Y12-R265W-VN and P2Y12R265W-VC were almost 4 times stronger than that of the wild type receptor as quantified in flow cytometry-based BiFC. Similar results were obtained in confocal microscopy. This suggests that these P2Y12 mutants form an increased number of dimers or oligomers with increased self-affinities. Conclusion: We demonstrate that P2Y12 forms constitutive homo-oligomers. Two mutations associated with bleeding disorders in patients have altered receptor-receptor interactions. Future investigation will explore the effect of mutations and receptor oligomers on G protein coupling and receptor: G protein stoichiometry.

A Retrospective Review Of Factor X Levels and Bleeding Risk In Patients With Amyloidosis

BackgroundBleeding is a common presentation of light chain AL amyloidosis mainly attributable to vascular fragility and impaired vasoconstriction also known as Amyloid Angiopathy. It has also been shown that acquired coagulation factor deficiencies such as Factor X can exacerbate this situation and can be the leading cause of mortality in these patients. We performed a retrospective review of Bleeding disorders in patients with AL amyloid from the Amyloid Database at The Houston Methodist Hospital between 2006 and 2013. MethodsWe performed a retrospective review extracting information from the Tumor Registry and the Medical Electronic Records by querying for the diagnosis of Amyloidosis. We obtained baseline demographics, laboratory data, diagnostic workup, treatment plan including bone marrow, Lung and Heart transplant, clinically documented bleeding events and overall outcomes. ResultsWe reviewed 411 patients who met the inclusion criteria. At the time of review, Amyloid typing was available in 95 patients out of which 85 were Al Amyloid. The baseline demographics included 213 males and 198 females, whose median age was 67; 238 were Caucasians while 77 were African Americans, 34 Hispanic, 12 Asian and 49 reportedly as others. Since the primary end point was review of bleeding, we sorted the groups based on the events into bleeders requiring ICU admission, bleeders without ICU admission and the non-bleeders. As shown in Figure 1, bleeders with ICU admission were 16 patients with a median PT of 19.77, median INR 1.6 and a low median factor X assay of 45% (range 70-120); Median BNP was 1285, serum creatinine 1.5, platelets 133, and Fibrinogen 356. From this group only 1 patient received a Heart and Lung Transplant.In the group of bleeders not requiring ICU admission there were 50 patients with a median PT of 16.2, median INR 1.128 and a low median factor X assay of 76%. Median BNP was 795 serum creatinine 1.37, platelets 126, and Fibrinogen 403.5. In this cohort 7 received bone marrow transplants, 3 received both Heart and Bone Marrow Transplants.In the group of nonbleeders, we had a total of 340 patients with a median PT of 15.7, median INR 1.2 and a low median factor X assay of 66. Median BNP was 240, serum creatinine 1.3, platelets 173, and Fibrinogen 409. In this cohort 16 received Bone Marrow transplant, 1 received lung Transplant and 10 received Heart Transplant. ConclusionEven though Amyloid Angiopathy is a major cause of bleeding, acquired factor X deficiency could potentially be reversible. There are reports of no correlation of diminished Factor X activity and severity of bleeding. Our data indicates that patients with very low factor X deficiency have a high risk of bleeding potentially requiring critical care support. Further statistical review of this data set will be presented at the American Society of Hematology, New Orleans 2013. Disclosures:No relevant conflicts of interest to declare.Bleeders w ICU AdmBleeders w/o ICU AdmNon BleedersNo. of Patients1650343Median Systolic BP111.5118126Median Diastolic BP67.56571Median Beta2-MicroGlobulin6.75.14.2Median Creatinine1.551.371.3Median BNP1285795240Median PT19.7716.215.7Median INR1.661.1281.2Median Factor X Assay45.57666Median PTT44.0433.1531.1Median Platelets133.69126173.58Median Fibrinogen346403.5409

The prevalence of underlying bleeding disorders in patients with heavy menstrual bleeding with and without gynecologic abnormalities

The purpose of this study was to assess the prevalence of underlying bleeding disorders in women with heavy menstrual bleeding (HMB) with and without gynecologic abnormalities. We performed a single-center prospective cohort study of 112 consecutive patients who were referred for heavy menstrual bleeding. Control subjects were 28 healthy volunteers who reported no HMB. Patients and control subjects had hemostatic testing in the first week after menstruation. Patients underwent gynecologic evaluation. The median age was 42.5 years (range, 17-55 years) in patients and 40.0 years (range, 25-55 years) in control subjects. Forty-six percent of patients had anemia; the median pictorial bleeding assessment chart score was 271. Seven percent of the control subjects with a subjectively normal menstruation had anemia. Twenty-six percent of patients had gynecologic abnormalities, which was considered to explain HMB. Overall, we found an underlying bleeding disorder in 29% of the patients, which was comparable for unexplained and explained HMB (31% vs 27%; P= .75). We diagnosed 6cases of Von Willebrand's disease, 4 cases of factor XI deficiency, and 1 case of factor VII deficiency. The only abnormalities that we found in control subjects were platelet aggregation defects (11% in control subjects vs 23% in patients). Patients had a significantly longer activated partial thromboplastin time compared with control subjects (26.5 vs 25.0 seconds; P= .001) that was caused by lower median levels of factor XI (100 vs 124 IU/dL; P < .001). Bleeding disorders play an equally important role in the cause of both unexplained and explained heavy menstrual bleeding. A novel finding is the occurrence of low, but not deficient, levels of factor XI.