Episodes Of Excessive Bleeding Research Articles

Three-dimensional assessment of the mandibular lingual foramina with implications for surgical and implant therapy: A multicentre cross-sectional study.

Treatment planning for dental implants in the anterior mandible is often complicated by the presence of vascular structures. The aim of our study was to investigate the prevalence, location and morphology of the mandibular lingual foramen (LF) through cone beam computed tomography (CBCT) scans and contribute to its anatomical knowledge in an Indian population. A total of 400 mandibular anterior CBCT scans from 4 centers were included in this retrospective analysis. The vertical distance from alveolar crest (Hcre) and inferior border of mandible (Hinf) to the LF, horizontal distance from lingual canal to labial cortical plate (LC-CP), length of the lingual canal (LLC) and diameter of the LF were measured. Data was analysed using Wilcoxon signed rank test and compared between median and lateral LF. 14 (3.5%) scans were excluded due to non-visualization of LF. A lateral LF was detected in 149 scans (38.6%), predominantly in the canine region (61.7%). Hcre was significantly higher for median LF (16.35±4.59mm) than lateral LF (12.94±3.92mm) (p<0.001), while Hinf did not show significant difference between median (11.38±3.62mm) and lateral (12.94±3.92mm) LF (p=0.0032). The LC-CP, LLC and diameter of LF averaged at 5.05±1.76mm, 6.26±1.82mm and 0.88±0.72mm respectively. The LF can be visualized in CBCT scans with a prevalence of 96.5%. This study stresses on the need for a CBCT, prior to surgeries in anterior mandible to avoid excessive bleeding episodes.

Day case locked anterior plating for distal radial fractures is safe with uninterrupted antithrombotic therapy.

We undertook a matched prospective cohort study over a 4-year period to examine the safety of continuing the administration of regular antithrombotic treatment with warfarin, clopidogrel or aspirin during day case surgical fixation of distal radial fractures. One hundred and one patients were identified and consented to participate in this study. There was only one reported complication: a superficial wound infection treated with antibiotics. No episodes of excessive bleeding were noted intraoperatively. All patients were discharged home on the day of surgery and there were no episodes of readmission, significant bleeding, haematoma requiring intervention, compartment syndrome or wound dehiscence. Complication rates were comparable with those of the matched cohort of patients undergoing the same procedure but who were not taking antithrombotic medications.Level of evidence: IV.

Long-term safety outcomes of prekallikrein (Fletcher factor) deficiency: A systematic literature review of case reports.

Background: Hereditary prekallikrein (Fletcher factor) deficiency is a rare condition characterized by a prolonged activated partial thromboplastin time. Inhibitors of plasma kallikrein have recently been approved for prophylaxis of hereditary angioedema and are under investigation for use in other indications. Objective: We attempted to conservatively assess the impact of long-term inhibition of this pathway by reviewing reported comorbidities in patients with hereditary prekallikrein deficiency. Methods: We searched several medical literature databases for publications that reported data from patients with hereditary prekallikrein deficiency (<10% of normal and/or shortening of activated partial thromboplastin time on increased incubation time). Data reporting of cardiovascular, bleeding, and autoimmune-related diseases were extracted. Results: Of 1966 publications screened, 45 publications (which represented 53 patients with prekallikrein deficiency) were included. Among 53 identified patients with prekallikrein deficiency, 25 were explicitly defined as asymptomatic, with no comorbidities mentioned in another three cases. Another 16 of the 53 patients were described as having undergone surgery or dental extractions with no complications. Cardiovascular comorbidities were reported in 19 patients, mainly hypertension (9 patients) and cerebrovascular ischemia or stroke (5 patients). Excessive bleeding episodes after surgery were reported in four patients. Autoimmune-related diseases were reported for three patients (two with Graves disease and one with systemic lupus erythematosus). Conclusion: This review identified patients with hereditary prekallikrein deficiency who reported a spectrum of health outcomes from asymptomatic to infrequent reports of cardiovascular, bleeding, and autoimmune comorbidities. The majority of the reports did not indicate any association between prekallikrein deficiency and comorbidities; however, additional observation is required to confirm the long-term safety of plasma kallikrein inhibition.

Long-term safety outcomes of prekillikrein (Fletcher factor) deficiency: A systematic literature review of case reports.

Hereditary prekallikrein (Fletcher factor) deficiency is a rare condition characterized by a prolonged activated partial thromboplastin time. Inhibitors of plasma kallikrein have recently been approved for prophylaxis of hereditary angioedema and are under investigation for use in other indications. We attempted to conservatively assess the impact of long-term inhibition of this pathway by reviewing reportedcomorbidities in patients with hereditary prekallikrein deficiency. We searched several medical literature databases for publications that reported data from patients with hereditaryprekallikrein deficiency (<10% of normal and/or shortening of activated partial thromboplastin time on increased incubationtime). Data reporting of cardiovascular, bleeding, and autoimmune-related diseases were extracted. Of 1966 publications screened, 45 publications (which represented 53 patients with prekallikrein deficiency) wereincluded. Among 53 identified patients with prekallikrein deficiency, 25 were explicitly defined as asymptomatic, with no comorbidities mentioned in another three cases. Another 16 of the 53 patients were described as having undergone surgery or dental extractions with no complications. Cardiovascular comorbidities were reported in 19 patients, mainly hypertension (9 patients) and cerebrovascular ischemia or stroke (5 patients). Excessive bleeding episodes after surgery were reported in four patients. Autoimmune-related diseases were reported for three patients (two with Graves disease and onewith systemic lupus erythematosus). This review identified patients with hereditary prekallikrein deficiency who reported a spectrum of health outcomes from asymptomatic to infrequent reports of cardiovascular, bleeding, and autoimmune comorbidities. The majority of the reports did not indicate any association between prekallikrein deficiency and comorbidities; however, additional observation is required to confirm the long-term safety of plasma kallikrein inhibition.

Blocking Protein S To Treat Hemophilia A

IntroductionProtein S (ProS) is a natural anticoagulant, acting as non-enzymatic cofactor for activated Protein C (APC) in the inactivation of activated factor V (FV) and factor VIII (FVIII), and for Tissue Factor Pathway Inhibitor (TFPI) in the inhibition of activated factor X (FXa). This dual role makes ProS a key regulator of the inhibition of thrombin generation as suggested by the phenotypes of ProS-deficient patients: venous thromboembolism at adult age for heterozygous patients and massive disseminated intravascular coagulation (DIC) incompatible with life for homozygous.Hemophilia A (HA) is an X-linked disorder caused by mutations in the F8gene, leading to deficiency or absence of FVIII, an essential component of the intrinsic pathway of blood coagulation.HA patients suffer from spontaneous excessive bleeding episodes affecting soft tissue, joints and muscles. Currently, recombinant factor FVIII (rFVIII) is the first line of HA therapy. Unfortunately, a major drawback observed in 30% of HA patients, is the generation of inhibitory alloantibodies that abrogate rFVIII activity, rendering the therapy ineffective. Another disadvantage is the short half-life of rFVIII. AimsTo enhance thrombin production in HA by specific blockage of ProS, thus overcoming the problems of rFVIII therapy. Lack of ProS cofactor activities on APC and TFPI might increase the generation of FXa, thus compensating for FVIII deficiency. Methods & ResultsHA mice are useful models to probe the effectiveness of procoagulant therapeutics as they recapitulate aspects of the human disease. Taking advantage from the availability of HA and ProS+/- mice, we aimed at generating ProS and FVIII double knock-out mice (HA-ProS-/-). To date ProS-/- mice were not viable and died in utero between E15.5-17.5 due to severe intracranial hemorrhages and consumptive coagulopathy. Surprisingly, by mating HA-ProS+/- mice we were able to rescue the lethal ProS-/- embryonic phenotype: HA-ProS-/-mice were viable and were found at the expected Mendelian frequency (45/192 neonates, 25%) with no increased mortality compared to HA mice.Plasma levels of FVIII and ProS further confirmed that HA-ProS-/- mice had comparable low FVIII and extremely reduced ProS compared to HA mice (1.8±0.5 vs 93.8±15.7 % respectively P=0.001) (mean±SEM). Analysis of complete blood counts established that these animals had a normal blood cell profile. Moreover, no differences were found in FV or FIX activity and in APTT and PT between HA and HA-ProS-/- mice. A decrease in fibrinogen levels in HA-ProS-/-when compared to HA mice (1.3±0.1 vs 1.7±0.1 g/L respectively, P< 0.001) was observed.To assess the in vivo effect of ProS-/- on HA mice hemostasis, a tail-clipping assay was used. In particular, blood loss assayed as blood volume lost over 10 min following a 4-mm tail transection significantly decreased to 158±11 uL (n=6) in HA-ProS-/- mice compared to HA and HA-ProS+/- (247 ±19 uL, n=10 and 239±11 uL, n=8 respectively, P<0.006). To further confirm that blocking ProS could improve the bleeding phenotype of HA mice, we infused 2.1 mg/kg of Ab against hProS on HA-ProS+/-mice, 2 minutes before tail clip. In line with our previous data, the reduction of ProS levels shortened blood loss to 196±10 uL (n=5, P<0.02).As recurrent joint bleeding is the most common manifestation of HA resulting in arthropathy, we challenged HA-ProS-/- in an acute hemarthrosis model. Joint swelling assessed as the ratio between punctured and non-punctured knees showed that HA-ProS-/- reached the biggest swelling at 24h (1.09±0.03, n=7 vs 1.28±0.08, n=7 HA) but remained stable until 72h in contrast to HA mice (1.11±0.02, n=7 vs 1.48±0.13, n=7 HA; P=0.018). Moreover, a relevant decrease of joint bleeding in HA-ProS-/- mice (0.5±0.2 vs 2.67±0.17; P<0.001) as assessed by visual bleeding score, was observed. ConclusionThese data provide the first evidence that blocking ProS has the ability to ameliorate HA as judged by in vivo improvement of bleeding phenotype in the tail clipping assay as well as in the acute hemarthrosis model. Strikingly, total FVIII deficiency does rescue the embryonic lethal phenotype of ProS-/- embryos and allows their survival without overt DIC. Together these results indicate that specific targeting of ProS favors the extrinsic pathway overcoming the intrinsic pathway deficiency, suggesting a new valuable tool for hemophilia therapy. Disclosures:No relevant conflicts of interest to declare.

Increased Blood Loss From Access Cannulation Site During Hemodialysis Is Associated With Anemia and Arteriovenous Graft Use

Blood loss from the access cannulation site during hemodialysis (HD) treatment is inevitable. Nevertheless, during HD, excessive blood loss from the cannulation site is not uncommon. The clinical characteristics associated with it and whether such blood loss could impact on patient outcomes is unknown. This pilot study aims to identify the prevalence and risk factors associated with excessive bleeding (≥ 4 mL/session) from dialysis access cannulation site during regular HD treatments. Stable end-stage renal disease patients receiving maintenance HD via arteriovenous fistula (AVF) or graft (AVG) were included in this study (N = 361). They were closely monitored for one month for the occurrence of excessive access bleeding during each HD session. A total of 4152 sessions of HD were performed during the study period and 143 patients (39.6%) had at least one episode of excessive bleeding from the vascular access (≥ 4 mL/session). Individuals experiencing excessive bleeding episodes had a significantly lower hemoglobin level, higher rate of diabetes, central venous stenosis, longer dialysis vintage, lower serum albumin level, longer hemostasis time and higher AVG and anti-platelet agent use (all P < 0.05). In the multivariable logistic regression model, longer dialysis vintage, central venous stenosis, lower hemoglobin level, and AVG usage were independently associated with occurrence of excessive access bleeding. AVG users also clustered with other risk factors for excessive access bleeding. Our study identified the novel associations between excessive cannulation site bleeding with dialysis vintage, anemia and AVG usage. The significance and impact of long-term chronic, intermittent bleeding from dialysis access should be further explored.

A 24-Year-Old Man with Previously Diagnosed Hemophilia

A 24-year-old Middle Eastern man diagnosed with hemophilia at the age of 4 or 5 years presented to the hematology clinic for follow-up after a recent hospitalization for excessive bleeding from an accidental knife cut. The patient reported a history of prolonged bleeding after teeth extractions, an upper gastrointestinal bleed 3 years previously, and excessive bruising since childhood. He denied hemarthroses but reported chronic pain in his ankles and joints. The patient reported having been treated for episodes of excessive bleeding with fresh frozen plasma (FFP)3 and factor VIII during past hospitalizations. Because of poor continuity of care, his disease had not been monitored or treated on an ongoing outpatient basis. The patient's family history is noteworthy for consanguineous parents (first cousins) and a sister who also experienced excessive bleeding, although her diagnosis was uncertain. Initial laboratory test results included a normal complete blood count, including platelets, a prolonged activated partial thromboplastin time (aPTT), and a prolonged prothrombin time (PT) (Table 1). Fibrinogen activity was normal. A 1:1 mixture of the patient's plasma with pooled normal plasma demonstrated full correction of the PT and aPTT, a result consistent with factor deficiency. View this table: Table 1. Patient's laboratory results (citrated plasma). ### ADDITIONAL PATIENT DATA AND DIFFERENTIAL DIAGNOSIS Patients with isolated hemophilia A, B, or C (due to deficiencies in factors VIII, IX, and XI, respectively) or factor VIII deficiency due to von Willebrand disease typically have a prolonged aPTT but a normal PT. In the absence of anticoagulation therapy or suspected vitamin K deficiency, a prolonged PT in this patient's initial workup should raise clinical suspicion for a bleeding disorder of a different etiology. Given the patient's clinically notable bleeding symptoms since childhood, a genetic disorder should be considered. The differential diagnosis includes dysfibrinogenemia, prothrombin deficiency, factor V deficiency, combined deficiency of factors V and VIII (F5F8D), factor X deficiency, and hereditary combined deficiency of …

Role of Transbronchial Biopsies in Pediatric Lung Diseases

To evaluate the role of transbronchial biopsies (TBBs) in pediatric lung diseases. We reviewed the records of TBBs performed in pediatric patients at the University of Florida between July 1996 and August 2003. The sample adequacy, diagnostic utility, and procedural complications of the two types of bronchoscopy apparatuses used to collect the samples were assessed and compared. A total of 429 TBB procedures were performed in 46 patients (age range, 2 months to 21 years) who had received a heart-lung or lung transplant and in 38 non-lung transplant patients (age range, 2 weeks to 18 years). For 86 procedures, the pediatric bronchoscope and forceps that fit in a 1.2-mm channel were used, and a small adult bronchoscope and 2.0-mm forceps were used for the remaining procedures. Adequate tissue samples were obtained in 85% of the procedures using a pediatric bronchoscope and in 97% using an adult bronchoscope. In the non-lung transplant patients, the biopsy findings were considered to be diagnostic in 58% of all procedures (adult bronchoscope, 64%; and pediatric bronchoscope, 50%), contributory in 21%, and noncontributory in 21%. In the lung transplant patients, treatable acute cellular rejection was diagnosed in 24% of the surveillance TBBs and in 47% of the TBBs performed as a result of clinical symptoms. Complications included five pneumothoraces and five episodes of excessive bleeding requiring the discontinuation of the procedure in three of the cases. Adequate lung tissue for histologic diagnosis can be obtained safely and effectively from pediatric patients of all ages via flexible bronchoscopy with TBB. The performance of bronchoscopy should be considered based on clinical indications, rather than on the age or size of the patient, when a tissue diagnosis is needed. When feasible, the use of an adult bronchoscope is preferable due to the higher diagnostic yield.

Factor VII Toyama (Thr 359 Met): A Homozygous Missense Mutation Causing Severe Type I Deficiency

We performed a DNA analysis on a patient with severe type I factor VII deficiency by the polymerase chain reaction amplification and a direct DNA sequencing method. The proband was a 66-year-old Japanese woman who had recurrent episodes of excessive bleeding after dental extraction. The functional and antigenic levels of plasma factor VII markedly reduced to 1.6% and 2% of normal, respectively. However, she had no serious symptoms such as intracranial or intraarticular hemorrhage. The analysis revealed that the patient was homozygous for a missense mutation, Thr (ACG) to Met (ATG) at codon 359 in the catalytic domain. Her deceased parents were first cousins, and their consanguineous marriage presumably resulted in the homozygosity in her. This patient was the first case of homozygote for the Thr359Met mutation, though heterozygotes for the mutation were previously found in an Italian family.

Use of low-dose low molecular weight heparin in hemodialysis

We investigated the lowest effective dosage of low molecular weight (LMW) heparin for hemodialysis in comparison to unfractionated (UF) heparin. Initial hemodialysis sessions were undertaken in 10 uremic patients with UF heparin of the dose habitually required for each patient. Four-hour hemodialysis sessions were then undertaken with LMW heparin (nadroparin) in a single bolus (200 anti-Xa unit Institut Choay/kg [aXaU IC/kg], 175 aXaU IC/kg, 150 aXaU IC/kg, or 125 aXaU IC/kg; two sessions for each dosage). Anti-Xa levels and activated partial thromboplastin time (APTT) were monitored hourly during dialysis. Fiber bundle volume of dialyzer was measured before and after dialysis. Urea clearance was determined at the onset and completion of dialysis. There were no episodes of excessive bleeding, clotting of dialyzers, or clots in air traps with UF heparin or LMW heparin. A 35% increase in APTT above baseline was observed in all dialysis sessions 1 hour after LMW heparin bolus, but the APTT decreased rapidly thereafter. The anti-Xa levels exceeded 0.5 U/mL for all sessions using LMW heparin irrespective of the dosage. No significant reduction of urea clearance was found in dialysis with either UF or LMW heparin. No reduction of fiber bundle volume of dialyzer was observed in dialysis with either UF or LMW heparin, although a small reduction (3%) was observed in dialysis with LMW heparin at 125 aXaU IC/kg. We concluded that the use of LMW heparin for hemodialysis is safe and effective as compared with UF heparin. The lowest effective dosage can be reduced to 125 aXaU IC/kg in high-risk patients to reduce hemorrhagic complications.

Thrombocytopenia and its management in the surgical patient needing multiple reconstructive procedures

Thrombocytopenic patients with surgically correctable lesions such as radial clubhands are too often repeatedly transfused with randomly pooled platelets. This is followed by a clinical rejection of the foreign protein and rapid destruction of the platelets. There may be excessive bleeding episodes. Tissue typing technics now available can provide antigenically compatible platelet concentrates which elicit few of these reactions. Therefore, multiple reconstructive procedures can be achieved with a greater safety margin than previously possible.

先天性第XIII因子欠乏症の急性壊疸性虫垂炎の手術例

A case of acute gangrenous appendicitis in a adult patient with congenital factor XIII deficiency is reported.T. K., 40 years old male, had had repeated episodes of excessive bleeding from wound and muscular hematoma since his childhood. The diagnosis of congenital factor XIII deficiency was established at the Department of Pediatrics, Nara Medical University in 1966 (Jap. J. Clin. Hemat. 15: 191, 1974).On Octover 22, 1973, the patient was admitted to Nara Medical University Hospital, because of nausea, abdominal pain and fever for one day.Physical examination revealed a moderate muscle defense, press pain of McBurney's point and positive Rosenstein's sign. No ecchymosis on the trunk and extremities. An appendectomy was performed under a cover of infusion with 6gm human fibrinogen preparations. The factor XIII activity rose to 10U/ml (20% of normal value) one hour after the infusion. The operation was done uneventfully. The appendix was purulent and gangrenous. On 7th postoperative day, the factor XIII activity demonstrated to be 2.5U/ml, and 4gm of human fibrinogen preparation was infused again. Shortly after the infusion threads were removed partially. No bleeding was observed. A complete removal of the suture was done on the 13th postoperative day, without an abnormal bleeding. On the 16th postoperative day, 4gm of human fibrinogen was given as the plasma level of factor XIII decreased to 2.5U/ml (5% of normal value). The wound healed normally. The patient was discharged after six week-hospitalization.