Routine Coagulation Studies Research Articles

Intravenous lipid emulsion interference in coagulation testing: an ex vivo analysis

Introduction Intravenous lipid emulsion is used in the rescue treatment of certain poisonings. A complication is interference with laboratory analyses. The aim of this study was to determine the impact of intravenous lipid emulsion on routine laboratory analysis of coagulation parameters ex vivo and determine if any of the analytical techniques remain reliable. Methods Samples were obtained from 19 healthy volunteers and divided in triplicate. One sample served as a control, and the other two were diluted to simulate the treatment of an average adult with Intralipid® 20 per cent Fresenius Kabi 100 mL (dilution-1) or 500 mL (dilution-2). Coagulation tests performed were prothrombin time, activated prothrombin time, D-dimer concentration and fibrinogen. Coagulation testing was performed by three techniques. Test-1 was performed on a Sysmex CN6000 analyzer. Test-2 was performed with a manual mechanical endpoint method using the semi-automated Stago KC4 Delta. Test-3 involved high-speed centrifugation before repeat testing on the Sysmex CN6000 analyzer. Results For test-1, only nine (47 per cent) samples in dilution-1 could be analyzed for coagulation tests, and no coagulation tests could be analyzed for dilution-2 because of lipaemia. For test-2 and test-3, all samples could be analyzed, and all results of both testing methods fell within the limits of the laboratory reference range. Discussion Difficulties in laboratory analysis of patients having received intravenous lipid emulsion are due to multiple factors. Most automated coagulation analyzers use optical measurements, which can be unreliable in the presence of a high intravenous lipid concentration. By altering the lipaemia in the testing solution using high-speed centrifugation or by using manual mechanical endpoint detection, we were able to obtain reliable results. These findings are limited by the use of an ex vivo method and healthy volunteers. Conclusions This ex vivo model confirms that Intralipid® interferes with routine coagulation studies. It is important that clinicians are aware and inform their laboratories of its administration.

Two Cases of Acute Direct Oral Anticoagulant Overdose Without Adverse Effect.

We report 2 pediatric patients who had acute overdoses of the direct oral anticoagulants medications. Both patients were managed conservatively; neither required reversal agents or blood products nor had any major or minor bleeding events. With therapeutic usage of direct oral anticoagulants, routine coagulation studies typically are considered insufficient measures of anticoagulation and the preferred chromogenic anti-Factor Xa assay is recommended but not widely available. Using a routine hybrid heparin anti-Factor Xa assay, 1 patient demonstrated a strong linear correlation up to a serum rivaroxaban concentration of 940 ng/mL.

Can an anti-Xa assay for unfractionated heparin be used to assess the presence of rivaroxaban in critical situations?

ObjectiveAlthough rivaroxaban has recently become widely used for thrombosis treatment, it is difficult for clinicians to make clinical decisions in critical situations, such as emergent surgery or interventions, because a specific anti-Xa assay is not available in many laboratories. This study assessed the relationships between rivaroxaban-specific anti-factor Xa activity (AXA) and unfractionated heparin (UFH)-specific AXA and determined the cutoff level for UFH-specific AXA in critical situations for patients undergoing rivaroxaban therapy. MethodsThirty-eight blood samples were collected from patients with cancer-associated thrombosis receiving rivaroxaban therapy. All samples were assessed using both rivaroxaban-specific and UFH-specific anti-Xa assays. Routine coagulation studies, including prothrombin time (PT) and activated partial thromboplastin time, were also conducted on the samples. ResultsA positive dose-dependent correlation between rivaroxaban-specific and UFH-specific AXA was evident (R = 0.97; P < .0001). Rivaroxaban-specific AXA was also positively correlated with PT (R = 0.95; P < .0001) but only weakly with activated partial thromboplastin time (R = 0.67; P < .0001). Patients with plasma rivaroxaban concentrations <100 ng/mL were found to have UFH-specific AXA <1.41 IU/mL and PT <17.3 seconds, with sensitivities of 100% and 93.3% and specificities of 87.0% and 95.7%, respectively. ConclusionsOur study demonstrates that UFH-calibrated AXA correlates strongly with plasma rivaroxaban concentration. This assay appears to be sensitive to the presence of rivaroxaban, which may be advantageous in the setting of assessing drug levels for critical events. These findings suggest that if a rivaroxaban-specific anti-Xa assay is unavailable, the chromogenic anti-Xa assay for UFH may be useful to assess the anticoagulant effects of rivaroxaban.

Periprocedural Major Bleeding Risk of Image-Guided Percutaneous Chest Tube Placement in Patients with an Elevated International Normalized Ratio.

To evaluate the incidence of major hemorrhage after image-guided percutaneous chest tube placement in patients with an abnormal international normalized ratio (INR) measured before the procedure. Between January 2013 and September 2017, 49 image-guided percutaneous chest tubes were placed in 45 adult patients who had an elevated INR of greater than 1.6. Data collected included routine serum pre-procedure coagulation studies, indication for chest tube placement, insertion technique, size of chest tube, and presence of complications after drain placement. Major bleeding complications were defined using the Society of Interventional Radiology classification system. Mean patient age was 62 years (range, 22-94 years), with median American Society of Anesthesiologists score of 4. Mean INR was 2.1 (range, 1.7-3), with 21 (43%) procedures with an INR between 1.7 and 1.9, 20 (41%) procedures with an INR between 2.0 and 2.4, and 8 (16%) procedures with an INR between 2.5 and 3.0. Computed tomography guidance was used for 27 (55%) procedures; ultrasound guidance was used for 22 (45%) procedures. Median size of chest tube was 10 Fr (range, 8-14 Fr) used in 27 (55%) procedures. No major bleeding complications were observed. There was a small, significant decrease in mean hemoglobin after the procedure (mean= 0.9g/dL; P < .0001), which correlated to increasing chest tube size (P= .0269). No major bleeding complications were observed after image-guided percutaneous chest tube placement in patients with an elevated INR. Major bleeding complications in these patients may be safer than initially considered, and this study encourages the conduct of larger trials for further evaluation.

Hypercoagulable Changes in Obese and Non-Obese Adolescent Females Initiating Combined Oral Contraceptives

Venous thromboembolism (VTE) is a rare but increasingly prevalent life-threatening pediatric disorder. Combined hormonal contraceptive use is a known risk factor for VTE. Combined oral contraceptive (COC)-related VTE risk is highest during the first 6 to 12 months of use and greater in obese individuals. Biological mechanisms for these increases in thrombotic risk are not well understood in adolescents. For the detection of meaningful hypercoagulable changes, routine coagulation studies are limited as they provide information exclusive to the initial period of clot development. Global coagulation assays have emerged as a superior marker of thrombotic risk. They offer details regarding the entire coagulation process and allow quantification of thrombin generation. The objective of the current study was to longitudinally evaluate thrombin generation in obese and non-obese adolescent females initiating COC.

Viscoelastic blood coagulation measurement with Sonoclot predicts postoperative bleeding in cardiac surgery after heparin reversal.

The aim of the study was to determine if Sonoclot with its sensitive glass bead-activated, viscoelastic test can predict postoperative bleeding in patients undergoing cardiac surgery at predefined time points. A prospective, observational clinical study. A teaching hospital, single center. Consecutive patients undergoing cardiac surgery (N = 300). Besides routine laboratory coagulation studies and heparin management with standard (kaolin) activated clotting time, additional native blood samples were analyzed on a Sonoclot using glass bead-activated tests. Glass bead-activated clotting time, clot rate, and platelet function were recorded immediately before anesthesia induction and at the end of surgery after heparin reversal but before chest closure. Primary outcome was postoperative blood loss (chest tube drainage at 4, 8, and 12 hours postoperatively). Secondary outcome parameters were transfusion requirements, need for surgical re-exploration, time of mechanical ventilation, length of intensive care unit and hospital stay, and hospital morbidity and mortality. Patients were categorized into "bleeders" and "nonbleeders." Patient characteristics, operations, preoperative standard laboratory parameters, and procedural times were comparable between bleeders and nonbleeders except for sex and age. Bleeders had higher rates of transfusions, surgical re-explorations, and complications. Only glass bead measurements by Sonoclot after heparin reversal before chest closure but not preoperatively were predictive for increased postoperative bleeding. Sonoclot with its glass bead-activated tests may predict the risk for postoperative bleeding in patients undergoing cardiac surgery at the end of surgery after heparin reversal but before chest closure.

Rotational thromboelastometry and multiple electrode platelet aggregometry in four patients with abnormal routine coagulation studies before removal of epidural catheters after major surgery: a case series and research study.

IntroductionRoutine coagulation tests have a low predictability for perioperative bleeding complications, and spinal hematoma after removal of epidural catheters is very infrequent. Thromboelastometry and point-of-care platelet aggregometry may improve hemostatic monitoring but have not been studied in the context of safety around epidural removal.MethodsTwenty patients who received an epidural catheter for major thoracoabdominal and abdominal surgery were included prospectively. In addition to routine coagulation tests, rotational thromboelastometry and multiple electrode platelet aggregometry were carried out.ResultsA coagulation deficit was suggested by routine coagulation tests on the intended day of epidural catheter removal in four out of 20 patients. Prothrombin time-international normalized ratio was elevated to 1.5 in one patient (normal range: 0.9 to 1.2) while rotational thromboelastometry and multiple electrode platelet aggregometry parameters were within normal limits. Activated partial thromboplastin time was elevated to 47 to 50 seconds in the remaining three patients (normal range 28 to 45 seconds). Rotational thromboelastometry showed that one of the patients’ results was due to heparin effect: the clotting time with the HEPTEM® activator was 154 seconds as compared to 261 seconds with INTEM. The three remaining patients with prolonged routine coagulation test results had all received over 1L of hydroxyethyl starch (Venofundin®) and thrombosis prophylaxis with low-molecular-weight heparin (enoxaparin). Rotational thromboelastometry and multiple electrode platelet aggregometrygave normal or hypercoagulative signals in most patients.ConclusionsThis case series is new in that it examines rotational thromboelastometry and multiple electrode platelet aggregometry postoperatively in the context of epidural analgesia and shows that they may be clinically useful. These methods should be validated before they can be used for standard patient care.

Preoperative localisation of parathyroid adenomas with mibi and ultrasonography: Is there an advantage of a combined approach?

s / International Journal of Surgery 11 (2013) 589e685 634 ABSTRACTS Clinical teaching was provided to junior AE Countess Chester Hospital, Chester, UK. Aim: To evaluate the outcome of sialendoscopy performed at Arrowe Park DGH, and to compare this to NICE findings. Method: A first cycle audit was performed. Retrospectively, the case notes of patients undergoing sialendoscopy between December 2004 and November 2008 were reviewed. Data was collected with regards to patient demographics, presentation, operative findings, length of stay, complications and outcome. A second cycle comparing the same parameters was subsequently undertaken for patients undergoing sialendoscopy between December 2008 to August 2012. Results: 51 patients in the 1st cycle and 61 in the second were reviewed. In both there is a female preponderance and an average age of 54 and 50 respectively. Swelling is the most prevalent presentation, and the most frequent gland affected is the left parotid. 61% of cases in the 1st cycle were daycase procedures, increasing to 90% in the 2nd. In comparison to NICE findings 80-88% of our patients had symptom relief (82-87% NICE). 2-3% suffered ductal wall perforation (9% NICE) and no patients had nerve damage (1 patient NICE). Our own complication rate also decreased between the two cycles. Conclusion: The outcome of sialendoscopy at our unit is improving over time and is comparable with NICE findings. 0417: PREOPERATIVE LOCALISATION OF PARATHYROID ADENOMAS WITH MIBI AND ULTRASONOGRAPHY: IS THERE AN ADVANTAGE OF A COMBINED APPROACH? Edward Ridyard , Derek Siau , Simon Hargreaves . University of Manchester, Manchester, UK; Royal Bolton Hospital, Farnworth, UK. Aim: To identify whether the combination of MIBI and ultrasound (USS) in localising a parathyroid adenoma preoperatively is more effective than either MIBI or USS used alone as the limitations of both imaging modalities are well documented. Method: Retrospective manual analysis of patients’ operative and medical notes (n1⁄476) reviewing the position of parathyroid adenoma localised via MIBI, USS and the subsequent confirmation of parathyroid adenoma on histological evaluation. Results: The combination of MIBI and USS provided a statistically significant improvement in preoperative localisation of parathyroid adenoma over MIBI or USS used alone (p1⁄40.033 and p1⁄40.043 respectively). There was no significant correlation between tumour volume and serum calcium or serum PTH (p1⁄40.234 and p1⁄40.742 respectively). There was a significant reduction in serum calcium and serum PTH postoperatively (p1⁄4 0.05). Conclusion: The value of CRP and coagulation tests in secondary PTH remains to be seen within our results. We suggest that routine CRP and coagulation studies should not be performed on PTH patients because it does not change management and isunlikely todiagnoseanunderling coagulopathy. If bleeding disorders are suspected clotting factors are a more appropriate investigation.

Do Elevated Hematocrits Prolong the PT/aPTT?

The Clinical and Laboratory Standards Institute guidelines require special processing of whole blood specimens with hematocrits greater than 55% due to the possibility of spurious prolongation of routine coagulation studies (PT, aPTT). As samples with hematocrits above 60% are rare at our institution, our study seeks to determine the effect of relative citrate excess on routine coagulation studies in samples with hematocrits of 60% to determine whether special processing is necessary. A calculated volume of 3.2% citrate was added to 1 mL aliquots of 40 whole blood samples in citrated tubes from adult patients to simulate a hematocrit of 60%. A dilutional control was created by adding an equivalent volume of saline to a separate 1 mL aliquot. Routine coagulation studies (PT, aPTT) were run on both samples on the STA Compact Analyzer in accordance with manufacturer instructions. While a paired Student's t-test demonstrated a clinically significant change in both PT and aPTT with the addition of citrate (p = 0.0002 for PT and p = 0.0234 for aPTT), clinical management would not have been altered by any observed change. More interestingly, we observed a shortening of 27/40 PTs and 23/40 aPTTs rather than the expected prolongation. Based on our data, no adjustment of citrate volume appears to be necessary in samples with hematocrits less than or equal to 60%.

Hemorrhage after Stereotactic Biopsy from Intra-Axial Brain Lesions: Incidence and Avoidance

With the introduction of stereotactic surgery in humans by Spiegel and Wycis in 1947 and the great advances in neuroimaging, image-guided stereotactic brain biopsy is the mainstay for diagnosis of intrinsic deep-seated brain lesions. Stereotactic biopsy is usually safe, and the reported rate of complications is minimal, with mortality being reported in less than 1% and significant morbidity occurring in less than 5%. The complication most often encountered after stereotactic biopsy is hemorrhage. A total of 150 patients (84 male and 66 female) with the mean age of 52.8 years having intra-axial brain lesions were included in the study. Image-guided (114 computed tomography [CT] and 36 magnetic resonance imaging [MRI]) stereotactic biopsy were performed by a specialized stereotactic neurosurgeon. Routine preoperative coagulation studies were performed in all patients. A workstation with multiplanar trajectory planning software was used. Serial biopsies were done with Sedan-type side cutting needle. Any detectable bleeding was analyzed by CT within 4 hours after procedure. All medical charts, laboratory results, preoperative imaging studies, and postoperative imaging studies were reviewed. A conclusive histopathological diagnosis was achieved in 147 patients (98%). In 7 patients (4.7%), hemorrhage was detected in post-biopsy CT scan (3.3% asymptomatic and 1.4% symptomatic). Hemorrhage occurred in patients with highly malignant tumors. There was no mortality. Using multiplanar image-guided trajectory planning and a small biopsy needle decreases the incidence of post-biopsy hemorrhage. Neurologically intact patients with no hemorrhage in post-biopsy CT scan could safely be discharged home at the same operative day.

Autoerythrocyte Sensitization Syndrome Treated with Kallikrein Inhibitor

To the Editor, I read the letter related to autoerythrocyte sensitization syndrome in a 7-year-old boy published in the Turkish Journal of Hematology [1]. I would like to remark on a few points that were not mentioned in that study. Autoerythrocyte sensitization syndrome was first described in 1972 by Karaca et al. from Turkey. They reported in detail on all characteristics in 2 patients, 19- and 23-year-old women [2,3], and a girl having severe emotional problems along with Gardner-Diamond syndrome was reported as the first childhood case in 1974 in our department [4]. The noteworthy characteristic of these ecchymoses is that they begin with local itching, burning, or pain before the lesions appear. Skin lesions are found to be correlated with periods of increased psychic stress and these patients are prone to hysteria, masochism, depression, and anxiety. The relationship between the syndrome and an underlying psychiatric disorder has been clearly emphasized. Although the etiological component of emotional stress in the formation of the lesions is not clear, the neuroimmune system is postulated as a mediator in the appearance of lesions. Gastrointestinal bleeding, epistaxis, hematuria, abdominal pain, diarrhea, nausea and vomiting, syncopal attacks, chest pain, headache, and menometrorrhagia are other findings or complaints in these patients [5,6]. The pathogenesis of autoerythrocyte sensitization syndrome remains unclear. Agle and Ratnoff identified polypeptides similar to bradykinin occurring in subcutaneous tissues in these patients [7,8]. Leiba et al. reported the possible role of bradykinin in the pathogenesis of the syndrome (DNA sensitization) [9].The kinin-kallikrein system is complex, with several bioactive peptides that are formed in many different compartments. This system plays a role in inflammation, coagulation, sodium homeostasis, sensations of pain, cardioprotective effects of proconditioning, and control of blood pressure [10]. Regulation in venous capillary tonus by fluctuations in the kinin-kallikrein system is suggested [6]. All of these studies suggest to us the treatment of the syndrome with bradykinin inhibitor. In our case, a 20-year-old married woman suffering from nausea, vomiting, abdominal pain, fatigue, and ecchymoses around the lower part of her extremities was admitted to the Department of Gastroenterology of the Ankara University School of Medicine. Characteristic skin lesions were present on the ventral surfaces of her legs. These lesions were painful, edematous, and of 2 to 6 cm in diameter. Physical examination was otherwise within normal limits. Routine laboratory tests and coagulation studies were normal. The skin lesions started spontaneously or following minimal trauma. They were characterized by itching and pain, followed by edematous ecchymoses. Intradermal injection of 0.1 mL of 60% suspension of washed red blood cells from the patient reproduced these characteristic skin lesions while the serum and plasma of the patient and saline were ineffective. The tests were repeated several times and found to be positive. She was diagnosed with autoerythrocyte sensitization syndrome and treated with kallikrein inhibitor aprotinin at 2000 IU/kg IV in 8 h [11]. After the treatment, all skin lesions disappeared and the patient received psychological support. The beneficial results obtained with kallikrein inhibitor in this case is suggestive of an important role of the kinin–kallikrein system on the pathogenesis of autoerythrocyte sensitization syndrome. Conflict of Interest Statement The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/ or affiliations relevant to the subject matter or materials included.

Combined congenital dysfibrinogenemia and factor VII deficiency from mutations in the FGB and F7 genes

Dysfibrinogenemia and factor VII (FVII) deficiency are rare congenital coagulopathies. In this report, the authors describe a man with both defects confirmed by molecular genetic tests. The patient was a 51-year-old man referred for prolonged prothrombin time (PT) that had been accidentally detected on preoperative screening. He had no history of bleeding tendency even on occasions of surgery. Routine coagulation studies revealed prolonged PT (1.53 INR) and thrombin time (42.2 s), and decreased fibrinogen level (57 mg/dl) and FVII activity (44%). Direct sequencing analyses were performed on FGA, FGB, and FGG genes to confirm dysfibrinogenemia and on the F7 gene to confirm FVII deficiency. As a result, the patient was shown to be heterozygous for a point mutation in exon 8 of the FGB gene (c.1475A > G, p.*492Trpext*12; Fibrinogen Magdeburg II) and for a missense mutation in exon 6 of the F7 gene (c.466G > A, p.Gly156Ser). To our knowledge, this is the first report on a case of combined dysfibrinogenemia and FVII deficiency confirmed by molecular genetic tests.

A case of acquired FXIII deficiency with severe bleeding symptoms

Acquired factor XIII (FXIII) deficiency due to an autoantibody against FXIII is a very rare, yet potentially life-threatening bleeding disorder. As the standard coagulation tests (prothrombin time and activated partial thromboplastin time) are normal, the specialized tests are required to make an accurate diagnosis. Here, we report a case of acquired FXIII deficiency with severe bleeding symptoms. A 75-year-old man was referred to our hospital because of severe bleeding tendency after a tooth extraction. Laboratory findings showed that routine coagulation studies were normal, but factor XIII (FXIII) activity was low (3%). The presence of FXIII inhibitor was detected with dot blotting studies. Although the bleeding tendency was very severe, it was successfully controlled by infusion of FXIII concentrates combined with immunosuppressive treatment (oral prednisolone). Fibrin cross-linking study showed the significant delay of the γ-chain dimer and α-chain polymer formation. Western blotting revealed the marked decrease in FXIII-A level. The mixing study of FXIII activity measured using amine-incorporation assay showed the incomplete inhibition pattern. There seems to be little agreement as to the treatment strategy of acquired FXIII deficiency. In this patient, the use of FXIII concentrates was very useful in the initial treatment of bleeding symptom. The use of steroids was also effective in increasing FXIII activity without any serious complications.

Transient Horner’s syndrome as sign of intrapetrous carotid dissection in a migrainous patient

We report the case of a patient that, during a migraine attack presented a transient Horner’s syndrome (HS), secondary to a spontaneous intrapetrous carotid artery dissection (IPCAD). Migraine is a common disorder with a pathophysiology that is incompletely understood. Migraine is considered a functional disorder of the brain, however, there are evidences linking migraine to the vascular system [1]. Endothelial dysfunction, altered vascular reactivity and hypercoagulability are reported in patients with migraine [2]. Migraine with aura seems to increase the risk of ischemic stroke [3] with unclear mechanisms. One link may be cervical artery dissection (CAD), since the association between M and CAD has been suggested [4]. Among CAD, spontaneous IPCAD is a rare occurrence, by far rarer than extracranial dissection, probably related to the anatomic localization that determinate the immobility of the petrous carotid portion fixed in the carotid canal [4]. A 36-year-old female presented with a moderate headache associated with 2-mm left ptosis and 2-mm anisocoria (left pupil smaller) without other neurological signs. The degree of anisocoria was enhanced in dim light, while visual fields and tonometry were normal. She had a positive family history for migraine without aura (MO). Past medical history was unremarkable. The patient did not present any cerebrovascular risk factor. When she was 17 years old, she started suffering from MO (ICHD-II criteria, [5]). The attacks were characterized by moderate, rarely severe, pulsating pain, aggravated by efforts. The pain was usually localized unilaterally in the periorbital right or left region and lasted 6–8 h. She reported nausea, rarely vomiting, phono and photophobia during the attacks. NSAIDs showed a good response. The attack associated with HS did not differ from the usual ones; pain was moderate, pulsating, localized in left fronto-temporal region and associated with phono and photophobia. Brain MRI with gadolinium and neck MRI with fat suppression were reported as negative; intracranial angio-MRI evidenced IPCAD on the left side (Fig. 1a, c). No etiological or predisposing factors to the dissection were disclosed, in particular, no clinical signs of Marfan’s syndrome were present. An occasional precipitating factor could have been the cough, secondary to a pharyngitis presented by the patient few days before hospital admittance. Routine blood counts, blood chemistry, coagulation studies, chest X-ray, electrocardiogram, transthoracic echocardiography and ophthalmology assessment were negative. A patent foramen ovale was excluded by a negative transcranial Doppler sonography with bubble test. Therapy with ASA was started; the subjective and neurological symptoms including HS disappeared in 48 h. A follow-up a month later evidenced a recanalization of the left carotid artery (Fig. 1b, d) and the patient was asymptomatic. The mechanisms by which migraine increase the risk of ischemic stroke could be resumed in the following points: (1) migraine may directly cause an ischemic stroke F. Maggioni (&) C. Disco G. Zanchin Department of Neurosciences, Headache Center, University of Padua, Via Giustiniani 5, 35128 Padua, Italy e-mail: ferdinando.maggioni@unipd.it

Acquired haemophilia a in a postpartum patient: diagnosis and management

Acquired haemophilia A is a potentially life threatening haemorrhagic disorder caused by spontaneous occurrence of autoantibodies directed against coagulation factor VIII. It has a mortality rate of up to 22%. We report a 40-year-old woman, para 5 who presented with 1 day history of painless haematuria. Seventy days earlier the patient experienced secondary postpartum haemorrhage following spontaneous vaginal delivery due to retained placenta, and was discharged well after ERPOC (evacuation of retained products of conception). Clinical examination was normal. Routine coagulation studies confirmed steady prolongation of activated partial thromboplastin time (APTT) up to 112 s with low factor VIII and high titre of factor VIII inhibitor (16.5 Bethesda units). Diagnosis of acquired haemophilia A was confirmed and she was treated with corticosteroid therapy, recombinant factor VII and intravenous immunoglobulin. The haematuria settled after 48 hours with normalisation of APTT and the level of factor VIII. After 2 months, the coagulation factor study revealed normal factor VIII level and disappearance of factor VIII inhibitors.

Epistaxis: when are coagulation studies justified?

Background:Epistaxis is a common emergency in otolaryngology. There is some evidence questioning the use of routine coagulation studies (prothrombin time and activated partial thromboplastin time (APTT)) in these patients, but...

Right lower lobectomy after right upper lobectomy for multiple metastases in lung cancer of the right lower lobe: Benefit of middle lobe preservation

Clinical Summary A 60-year-old woman with lung cancer underwent right upper lobectomy. The tumor specimen was a well-differentiated adenocarcinoma, pathologic stage IA (T1 N0 M0). Multiple slow-growing nodules were noted in the right lower lobe 4 years postoperatively. Recurrent lesions are generally multiple and disseminated, and additional surgical intervention is not usually indicated. However, no nodules were apparent in other lobes during 1 year of follow-up. The patient was therefore referred to our department for surgical treatment. Routine blood biochemistry and coagulation studies yielded normal results and carcinoembryonic antigen level was 2.6 ng/mL. A chest computed tomographic scan from 4 years earlier showed the primary lung cancer as a solid tumor in the right upper lobe (Figure 1, A), compared with the scan of multiple nodules limited to the right lower lobe for the metastases (Figure 1, B). These multiple tumors showed no uptake on a fluorodeoxyglucose positron emission tomographic scan. Transbronchiolar lung biopsy was not performed owing to patient refusal. No extrathoracic metastatic lesions were identified. Preoperative forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1.0) were 2420 mL and 1510 mL, respectively. We evaluated predicted results of completion pnuemonectomy using perfusion scintigraphy and pulmonary artery obstruction testing. Predicted FVC and FEV1.0 after completion pneumonectomy were 1114 mL and 695 mL, respectively. Obstruction of the right pulmonary artery yielded a pressure of 19 mm Hg. Video-assisted right lower lobectomy was performed, preserving the middle lobe. Adhesion of the lower lobe to the chest wall was easily removed by the thoracoscopic view. The middle lobe was also adherent to the chest wall and helped to prevent middle lobe torsion. On final pathologic examination, the specimen from the lower lobe was characteristic of metastatic adenocarcinoma from the previous lung cancer of the right upper lobe (Figure 1, C and D). Postoperative FVC and FEV1.0 were 1570 mL and 1200 mL, respectively. Perfusion scintigraphy showed 391,199 (21.7%) of 1,801,504 counts for the preserved middle lobe (Figure 2). Respiratory function after right upper and lower lobectomies preserved more than half of the original respiratory function. The postoperative course was uneventful. Chest computed tomographic imaging after 1 year of preservation of the middle lobe showed adequate volume without emphysematous change. After 17 months of follow-up, the patient is doing well with no evidence of disease or requirement for additional oxygen support.

Time to Hemostasis after Traction Removal of Tunneled Cuffed Central Venous Catheters

Many patients undergo placement of tunneled cuffed central venous catheters (TCCVCs) for indications including administration of medical therapy and hemodialysis. They are removed when no longer needed or if there is a device complication. There is no consensus regarding the necessity of routine preremoval coagulation studies or platelet count, so this study was performed to determine if abnormal coagulation status affects the time to hemostasis (TH) after traction removal of TCCVCs. Adult patients referred to our group for removal of a TCCVC placed via a jugular or subclavian route were considered candidates for inclusion. Blood was submitted for evaluation of prothrombin time (PT) and International Normalized Ratio (INR), activated partial thromboplastin time (aPTT), and platelet count. Catheters were removed with the traction technique, and presence of hemostasis was assessed at 5-minute intervals of manual compression. Between November 19, 2001, and April 20, 2004, 179 subjects were enrolled and completed the study. There were 165 subjects in whom TH was within the first 5-minute interval and 14 in whom more than 5 minutes was required. Statistically significant factors associated with prolonged TH were primary diagnosis of end-stage renal disease (P = .005), use of antiplatelet agents (P = .03), and procedure performed by a "low-volume" operator (P = .002). Routine preremoval evaluation of coagulation parameters is not necessary. Patients who are likely to have abnormal platelet function but not abnormal platelet number appear to be at risk for prolonged TH, but even in those cases, the THs are rarely more than 15 minutes.

Heparin-like anticoagulant associated with multiple myeloma and neutralized with protamine sulfate

A 55-year-old man with multiple myeloma developed sustained bleeding after bone marrow aspiration and cutaneous bleeding. Routine coagulation studies revealed a prolonged activated partial thromboplastin time and thrombin time (> 60 s) with a normal reptilase time. Further evaluation showed failure of the activated partial thromboplastin time to correct completely in a 1: 1 mixture with normal plasma. Treatment of the patient's plasma in vitro with protamine sulfate normalized the thrombin time. The presence of a heparin-like anticoagulant was suspected. The plasma heparin level was 0.73 IU/ml. Intravenous infusion of protamine sulfate appeared to neutralize the anticoagulant activity and stop the bleeding. The cancer cells themselves or the invasive nature of this type of cancer might result in a massive release of a heparinoid. Such coagulopathy appears to be a rare mechanism of bleeding and it is an important entity to consider since it is potentially reversible with protamine sulfate.

Case Report of an Acquired Factor Xiii Inhibitor: Diagnosis and Management

A 57-year-old man presented with a spontaneous upper-extremity hematoma and compartment syndrome. The patient experienced excessive bleeding following evacuation of the hematoma, and the results of routine coagulation studies were normal. Factor XIII activity was undetectable using a photometric assay, and the presence of an inhibitor was detected with mixing studies. Bleeding was controlled with infusions of fresh frozen plasma and cryoprecipitate. Cyclophosphamide was started on the 16th hospital day, and four weekly doses of the monoclonal anti-CD20 antibody, rituximab, were begun 3 weeks later. One week after the initial dose of rituximab, the inhibitor was no longer detectable and the factor XIII level increased to 28%. After completion of the rituximab therapy, the factor XIII activity was 58% with no inhibitor present. This case illustrates the need to check for unusual defects such as factor XIII deficiency if a bleeding tendency is evident—even if routine studies are unrevealing.