Prolongation Of Partial Thromboplastin Time Research Articles

Acquired hemophilia A in a case of purple urine bag syndrome

The rare hemorrhagic disorder known as acquired hemophilia A (AHA) is brought on by the spontaneous development of autoantibodies against coagulation factor VIII (FVIII). It may be secondary to autoimmune diseases or cancers, or it may be idiopathic. Less than 10% of cases may have an infection as a secondary cause. We present the case of a 90-year-old anemic woman who was admitted to the hospital. She contracted a urinary tract infection (UTI) while in the hospital, and her urine took on a distinct purple hue. She had poor hemorrhagic manifestations and a prolonged partial thromboplastin time. After ruling out autoimmune and neoplastic causes, we diagnosed AHA as a result of a UTI caused by Enterococcus faecalis.

Medical History and Preoperative Coagulation Profile as Predictors of Outcomes in Elective Spinal Surgery: A Meta-Analysis

In patients with unremarkable medical history, comprehensive preoperative hemostasis screening in elective neurosurgery remains debated. Comprehensive medical history has shown to be noninferior to coagulation profile to evaluate surgical outcomes. This study aims to evaluate the predictiveness of preoperative coagulation screening and medical history for surgical outcomes. Databases were searched until April 2023 for observational cohort studies that reported preoperative hemostasis screening and clinical history prior to elective neurosurgical procedures. Outcomes of interest included postoperative transfusion, mortality, and complications. Pooled relative risk ratios (RRs) were analyzed using random-effects models. Out of 604 studies, 3 cohort studies met our inclusion criteria, adding a patient population of 83,076. Prolonged partial thromboplastin time (PTT; RR=1.42, 95% confidence interval [CI]=1.14, 1.77, P=0.002), elevated international normalized ratio (INR; RR=2.01, 95% CI=1.14, 3.55, P=0.02), low platelet count (RR=1.58, 95% CI=1.34, 1.86, P<0.00001), and positive bleeding history (RR=2.14, 95% CI=1.16, 3.93, P=0.01) were associated with postoperative transfusion risk. High PTT (RR=2.42, 95%CI=1.24, 4.73, P=0.010), High INR (RR=8.15, 95% CI=5.97, 11.13; P<0.00001), low platelet count (RR=4.89, 95% CI=3.73, 6.41, P<0.00001), and bleeding history (RR=7.59, 95% CI=5.84, 9.86, P<0.00001) were predictive of mortality. Prolonged PTT (RR=1.53, 95% CI=1.25, 1.86, P=<0.0001), a high INR (RR=3.41, 95% CI=2.63, 4.42, P=< 0.00001), low platelets (RR=1.63, 95% CI=1.40, 1.90, P=<0.00001), and medical history (RR=2.15, 95% CI=1.71, 2.71, P=<0.00001) were predictive of complications. Medical history was a noninferior predictor to coagulation profile for postoperative transfusion, mortality, and complications. However, our findings are mostly representative of elective spinal procedures. Cost-effective alternatives should be explored to promote affordable patient care in patients with unremarkable history.

Impact of Enteral Nutrition Support on Biochemical and Nutritional Biomarkers and Chemotherapy Complications in Children with Acute Lymphoblastic Leukemia in the Induction Therapy Stage

This research attempted to explore the effect of induction therapy on changes in nutritional status and chemotherapy complications in children with acute lymphoblastic leukemia. One hundred newly diagnosed patients were randomly assigned to observation and control groups, each comprising 50 participants. Both groups received chemotherapy; however, their dietary regimen differed. The control group received a conventional low-fat diet, while the observation group received one-fourth to one-third of daily total energy intake through enteral nutrition preparations and the remaining energy intake through a conventional low-fat diet until the end of the induction remission period. This study revealed no significant differences between the two groups regarding mid-arm circumference, skinfold thickness, body mass index, and serum albumin levels before and after therapy. After therapy, total protein and prealbumin levels were significantly higher in the observation group compared to the control group. Moreover, the incidence of neutropenia and anemia, average numbers of transfusions of red blood cells and platelets, alanine aminotransferase, activated partial thromboplastin time prolongation, and the incidence of fever were not significantly different between the two groups after therapy. In conclusion, enteral nutrition support elevated selected biochemical markers, but it did not substantially alter nutritional biomarkers and hematological and non-hematological complications.

Acquired Postpartum Hemophilia A Presentation of Severe Hematuria: A Case Report

BACKGROUND: Acquired hemophilia A (AHA) is a rare, severe bleeding disorder caused by the development of autoantibodies against FVIII that may be idiopathic or secondary to medical conditions. Postpartum AHA can occur as early as 1–4 months after delivery or as late as 1-year postpartum. CASE REPORT: A 20-year-old female presented with vaginal bleeding 20 days after delivery, then ecchymotic patches developed 2 months later, followed by hematuria 2 months after that. Laboratory investigation revealed isolated, prolonged partial thromboplastin time that was not corrected by mixing 50:50 with fresh normal plasma. FVIII activity was markedly deficient, with a high titer of immediate-acting FVIII inhibitor antibodies. CONCLUSION: The case was diagnosed as postpartum AHA with a good response to the combined steroids and cyclophosphamide treatment.

A Patient with Severe Fever with Thrombocytopenia Syndrome, Activated Partial Thromboplastin Time Prolongation, and Transient Antiphospholipid Antibodies.

A prolonged activated partial thromboplastin time (APTT) is observed in patients with severe fever with thrombocytopenia syndrome (SFTS) and is one of the risk factors for severe disease. The mechanism underlying a prolonged APTT is largely unknown. The presence of antiphospholipid (aPL) antibodies in various viral infections has been documented but never reported in a patient with SFTS. We herein report the first SFTS patient with APTT prolongation and concurrent transiently positive aPL antibodies (lupus anticoagulants and anticardiolipin antibodies) with no coagulation factor deficiency.

Myasthenia gravis and independent risk factors for recurrent infection: a retrospective cohort study

BackgroundApproximately 10% to 20% of myasthenia gravis (MG) patients have experienced a myasthenic crisis (MC), which contributes to morbidity and mortality. MC triggered by infection is associated with poor outcomes. However, there is a lack of prognostic factors that clinicians can utilize to target interventions for preventing recurrent infection-triggered MC. This study aimed to characterize clinical manifestations, comorbidities, and biochemical profiles associated with recurrent infection-triggered MC in MG patients.MethodsThis retrospective study included 272 MG patients hospitalized with an infection requiring at least 3 days of antibiotics from January 2001 to December 2019. Patients were further stratified into non-recurrent or recurrent infection groups. Clinical features such as gender, age, concomitant diseases, acetylcholine receptor antibodies and biochemical data (including electrolytes and coagulants), muscle strength of pelvic and shoulder girdle, bulbar and respiratory function, management with an endotracheal tube, Foley catheter, or plasmapheresis, duration of hospitalization, and culture pathogens were recorded.ResultsThe recurrent infection group was significantly older than the non-recurrent group (median age, 58.5 versus 52.0 years). Pneumonia was the most common infection and Klebsiella pneumoniae was the most common pathogen. The presence of concomitant diabetes mellitus, activated partial thromboplastin time prolongation, the duration of hospitalization, and hypomagnesaemia were independently associated with recurrent infection. The presence of deep vein thrombosis, thymic cancer, and electrolyte imbalances i.e., hypokalemia, and hypoalbuminemia were significantly associated with a risk for infection. The influence of endotracheal intubation, anemia, and plasmapheresis during hospitalization were inconsistent.ConclusionsThe independent risk factors for recurrent infections in MG patients identified in this study include the presence of concomitant diabetes mellitus, hypomagnesaemia, activated partial thromboplastin time prolongation, and longer duration of hospitalization, highlighting the need for targeted interventions to prevent recurrent infections in this population. Further research and prospective studies are warranted to validate these findings and refine interventions for optimizing patient care.

Evaluation of Antioxidant, Antihemolytic Activity, Analgesic and Anti-Inflammatory Potential of Aristolochia clematitis Extracts

There is an increasing interest in medicinal plants to find natural remedies relatively safer than synthetic alternatives. The present study reports the evaluation of the in vitro and in vivo biological properties of crude extract (CrE), hexane (HeE), ethyl acetate (EAE) and aqueous (AqE) fractions of Aristolochia clematitis. The polyphenol and flavonoid content were determined and varied from 15.77 ± 0.28 to 93.62 ± 1.63 mg EGA/g, and 5.71 ± 0.1 to 13.53 ± 0.15 µg EQ/mg, respectively. Crude extract (CrE) and ethyl acetate (EaE) showed the highest scavenging activity of DPPH radicals (IC50 = 50.66 ± 1.41 and 69.57 ± 0.38 µg/mL) and hydroxyl radicals (IC50 = 0.894 ± 0.042 and 0.905 ± 0.890 mg/mL), reducing power (113.85 ± 0.5 and 82.45 ± 0.13 mg/mL) and the ability to inhibit β-carotene oxidation (76.13 ± 0.93, 69.18 ± .95 %). All extracts have the ability to protect red blood cells from AAPH peroxyl radicals and significantly increase hemolysis time compared to vitamin C. Tested on normal human plasma at a concentration of 50 and 100 mg/mL, these extract prolonged prothrombin (PT) and partial thromboplastin (aPTT) times. In addition, CrE tested at doses of 150 and 300 mg/kg, showedpotent antinociceptive effect (40.68 ± 3.84 and 66.61 ± 4.71%) and anti-inflammatory activity (65.71 ± 1.41 and 63.89 ± 2.17%). The results support the use of this plant in traditional medicine and suggest that it may contain phytochemicals that have the potential to be active agents as antioxidants, anticoagulants and analgesics.&nbsp

Rare diagnosis of coexistent antiphospholipid syndrome and systemic lupus erythematosus in a male patient with successful management: a case report.

A 28-year-old male, referred to our hospital for the assessment of chest pain. Past medical history was significant for extensive deep venous thrombosis despite the appropriate management with a therapeutic dose of direct-acting oral anticoagulant. Prolonged partial thromboplastin time was not corrected by mixing study along with positive lupus anticoagulant, anticardiolipin, and B-2 glycoprotein antibodies. In addition, antinuclear antibodies, anti-DNA antibodies, and direct Coombs were positive with decreased levels of C3. The patient was diagnosed with SLE with brain, heart, and kidney involvement in the setting of antiphospholipid antibody syndrome. He was treated successfully with full recovery. SLE and APS both have sneaky ways of manifestation. Ineffective diagnosis and therapy could cause irreversible organ damage. Clinicians should have a high index of suspicion for APS, particularly in young patients who approach with spontaneous or unprovoked thromboses or unexplained recurrent early or late pregnancy loss. Anticoagulation, modifying cardiovascular risk factors, and identifying and treating any underlying inflammatory diseases are all part of the multidisciplinary care that is needed for management. Although male affection is rare, SLE and APS should be considered in male patients as these conditions tend to be more aggressive than in the female.

Cyclosporine treatment for steroid-resistant nephrosis complicated with acquired hemophilia A: a case report.

A 12-year-old girl with steroid-resistant nephrosis (SRN) was admitted complaining of pain in her right leg and an ultrasound showed a hematoma in her right calf. The coagulation profile revealed partial thromboplastin time prolongation and high titers (156 BU) of anti-factor VIII inhibitors were observed. Where half of the patients with antifactor VIII inhibitors were associated with underlying disorders, additional tests were performed that rule out secondary causes. This patient with long-standing SRN, who was on a maintenance dose of prednisone for six years, was complicated with acquired hemophilia A (AHA). In different to the last recommendations of AHA treatment, we preferred using cyclosporine; which is considered the initial second-line therapy for children with SRN. Complete remission was achieved of both disorders after a month with no recurrence of nephrosis or bleeding events. To our knowledge, nephrotic syndrome with AHA was reported in only three patients, two cases after remission and one during a relapse but no one were treated with cyclosporine. The authors encountered the first case of cyclosporine treatment for AHA in a patient with SRN. This study supports the use of cyclosporine to treat AHA, especially with nephrosis.

Activated Partial Thromboplastin Time or Prothrombin Time Prolongation During Rivaroxaban Administration: Clinical Risk Factors and Outcomes Analysis.

Activated partial thromboplastin time (aPTT) or prothrombin time (PT) is often detected after rivaroxaban administration, and it is known that aPTT or PT can be prolonged or normal. However, the clinical risk factors and outcomes of prolongation were unknown. In a single-center, retrospective case-control study, adult inpatients who had aPTT/PT tested before and after administration of rivaroxaban during a designated 12-month period were eligible for inclusion. Depending on whether their aPTT/PT was prolonged, patients were allocated to the prolonged case or normal control group. Demographics, rivaroxaban indications and daily dose, and laboratory values were compared. Multivariate logistic regression was used to identify independent risk factors. The changes in laboratory values and clinical outcomes were analyzed. A total of 155 patients were included in the study among which 54 (34.84%) were reported to have either or both aPTT/PT prolonged. The average prolongation time of PT was between 0.8 and 0.9 s, and 1.8 and 3.5 s for aPTT. Multivariable regression modeling showed that height (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.02-1.22, P = .02) and human albumin replacement (OR 3.19, 95% CI 1.05-9.74, P = .04) were independent risk factors for aPTT/PT prolongation. The incidence of bleeding events and changes in laboratory values were similar between the groups. Patient height and receiving human albumin replacement were independent risk factors for aPTT/PT mild prolongation caused by rivaroxaban. The prolongation was not associated with an increased occurrence of bleeding events.

Coagulation Disorder’s in SARS-CoV-2 Patients

Context: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease of 2019 (COVID-19). Pulmonary manifestations have been identified as the common symptom, and patients present a wide range of hematologic changes depending on the flow of the diseases. The interpretation and treatment of hematological complications in COVID-19 patients are very challenging. There are limited guidelines thus far due to the novelty of the disease. Evidence Acquisition: This review summarizes the hematological findings (platelet and coagulation/fibrinolytic) in COVID-19 patients and discusses possible mechanisms for their changes. Results: The results showed that the common findings were thrombocytopenia, elevated D-dimer levels, and prolonged prothrombin time (PT) and partial thromboplastin time (PTT) in severe patients. Conclusions: Attention to hematological changes may be helpful biomarkers in diagnosing and determining patients needing intensive care, as well as monitoring the treatment process and treatment effects on COVID-19 patients.

A Case Series of Immune Flare and Lupus Anticoagulant Following COVID-19 Vaccination

Background: Vaccination against COVID-19 has garnered concerns for unusual post-vaccination complications. We present 2 cases of immune flare following COVID-19 vaccination. Case Report: Our first patient was a 53-year-old male who presented with a swollen left leg, hypoxia and palpitations after a trans-Atlantic flight. Chest computed tomography showed bilateral subsegmental pulmonary emboli, with no evidence of right heart strain and Doppler ultrasonography of the lower extremities showed significant clot burden in the left femoral, popliteal, tibial and peroneal veins. Workup revealed thrombocytopenia of 81,000/μL (normal range [NR] 150,000-450,000/μL), elevated D-dimer of 6.25 μg/ml (NR < 0.5 μg/ml), elevated partial thromboplastin time at 94 seconds without heparin. Mixing studies corrected partially to 60.9 seconds (NR 22.5-39.4), indicating the presence of an inhibitor, and lupus anticoagulant was confirmed with dilute Russell viper venom ratio of 3.66 (NR 0.00-1.20) and silica clotting time ratio of 3.95 (NR 0.00-1.22). Anti-beta-2 glycoprotein and anti-cardiolipin antibodies, factor V Leiden mutation, prothrombin G20210A mutation, protein C and protein S were negative. He received 2 doses of the ChAdOx1 nCoV-19 adenoviral vaccine 6 weeks previously. Due to suspicion for vaccine-induced thrombotic thrombocytopenia, enzyme-linked immunoassay for anti-platelet-factor 4 antibody was tested, which was negative. Immediate anticoagulation therapy with low-molecular weight heparin was started and then switched to rivaroxaban. Our second patient was an 18-year-old male who presented with 2 weeks of right-sided lower chest pain. The cardiopulmonary workup was negative, with a computed tomography of the chest showing a borderline enlarged spleen at 13 cm, and hepatic steatosis. He was taking indomethacin for slipped rib pain and was less mobile than usual. One week later, he developed left posterior thigh pain extending down the posterior calf and was found to have totally occluding left leg deep venous thrombosis from femoral vein mid to distal, popliteal, posterior tibial, peroneal, gastrocnemius and soleal veins. Workup was significant for prolonged partial thromboplastin time at 78 seconds, which partially corrected to 62 seconds with mixing studies, elevated C-reactive protein of 5.4, positive antinuclear antibodies (1:1280), normal complement (C3 and C4) and negative RF, SS A/Ro, SS B/La, RNP, smooth muscle, LKM antibodies. He started anticoagulation with low-molecular weight heparin, which was transitioned to apixaban. His family history was significant for lupus in his aunt and grandmother; however, there was no family history of thrombosis. He had received the third mRNA COVID vaccine 2 weeks prior to presentation. Additional workup revealed positive lupus anticoagulant, beta-2 glycoprotein, cardiolipin antibodies, and he was started on warfarin with a target international normalized ratio of 2-3 and repeat testing 3 months later revealed persistent elevation, indicating antiphospholipid syndrome. Although there was low suspicion for vaccine induced thrombotic thrombocytopenia, heparin-induced thrombocytopenia panel was performed and was negative. Discussion: Multiple SARS-CoV-2 vaccines were rapidly developed and approved, but long-term effects are unknown. Recombinant adenoviral vector-based vaccines raised concerns for an unusual post-vaccination coagulopathic syndrome with anti-platelet-factor 4 antibodies seen in 90% of probable and definite cases of vaccine-induced thrombotic thrombocytopenia (Pavord et al). Positive lupus anticoagulant has been noted with severe COVID-19 (Tung et al); however, our first patient had no history of COVID-19. This presentation was attributed at the time to a pro-inflammatory state induced by vaccination that may have caused lupus anticoagulant titers to rise leading to thrombosis as seen in this case. Autoimmune manifestations after COVID-19 vaccination are thought to be due to molecular mimicry, autoantibodies, vaccine adjuvants and a pro-inflammatory cascade among multiple other mechanisms (Chen et al). Similar to other viral infections, COVID-19 and additionally vaccination against it may lead to flare of immune mediated diseases (Talotta et al) as what occurred in our second patient with predisposition to hypercoagulable state given his family history of systemic lupus erythematosus.

A Two Part Case Series on Acquired Hemophilia A

Abstract Introduction/Objective Acquired Hemophilia A is a rare condition with an incidence of 1 per 1.5 million per year. The average age at presentation is 74 years. It is due to spontaneous production of IgG autoantibodies that target endogenous factor viii. This disease should be considered when a patient presents with bleeding, an abnormal prolongation of activated partial thromboplastin time and /or no prior personal or family history of bleeding. Autoimmune disorders and malignancy are common associations. Pregnancy and surgery are common presenting scenarios. Methods/Case Report Case 1: 71 year old female with a history of deep venous thrombosis, and rheumatoid arthritis. Patient presented to the emergency department with a hemoglobin of 4.7 and coagulation studies showed a prolonged partial thromboplastin time of 119 seconds. Imaging revealed retroperitoneal bleeding. A mixing study showed no correction of partial thromboplastin time. The patient was treated with packed red blood cell transfusions until hemodynamically stable. Further coagulation studies revealed a factor VIII activity of 3L and factor VIII inhibitor level of 103 bethesda units. This confirmed suspicion of an acquired factor VIII inhibitor associated with the patient’s rheumatoid arthritis as the source of abnormal lab values and bleeding. Patient was treated with recombinant factor VIIa, novoseven, along with continuous prednisone and cyclophosphamide. Case 2: 82 year old male with history of IgG Kappa Monoclonal Gammopathy of Undetermined Significance. Patient presented with gastrointestinal bleeding and 4g/Dl hemoglobin. He received 5 units of packed red blood cells. Sigmoidoscopy revealed a rectal ulcer causing lower gastrointestinal bleeding. An advanced coagulation study revealed factor VIII activity of 1%, and inhibitor levels of 17 bethesda units. Patient was started on prednisone initially, followed by cyclophosphamide. However, bleeding continued. He was treated with 6 units of recombinant factor VIIa and packed red blood cell transfusions as required to keep hemoglobin levels at 7g/Dl. He was continued on prednisone at an increased dosage and discharged. Results (if a Case Study enter NA) NA. Conclusion Acquired Hemophilia A is a rare disease. It should be suspected anytime there is unprecedented bleeding and/or unexplained prolongation of partial thromboplastin time. It is diagnosed with factor VIII panel, including inhibitor. Treatment includes immunosuppresants, intravenous immunoglobulins, and recombinant factor VIIa.

The use of carglumic acid in hyperammonemia secondary to bacterial overgrowth in lately diagnosed Hirschsprung disease

Hirschsprung disease is associated with significant bacterial proliferation and colonic dysbiosis leading to life threating hyperammonemia. In this report, we highlight the use of carglumic acid; a synthetic ammonia scavenger in hyperammonemia secondary to bacterial overgrowth in Hirschsprung disease. A 33-month-old female patient with a history of delayed passage of meconium presented with constipation, vomiting, abdominal distention, and an altered level of consciousness. Physical examination revealed a puffy face, non-pitting edema and distended, rigid, non-tender abdomen with faint bowel sounds. Further investigations showed anemia, hypoalbuminemia, hyperammonemia, prolonged prothrombin time and partial thromboplastin time alongside a normal liver enzymes panel. Abdominal X-ray imaging revealed severely dilated bowel loops reassembling obstruction and impending perforation. A lower gastrointestinal contrast study revealed a classical picture of Hirschsprung disease with a transition zone at the rectosigmoid. Urgent surgical intervention was performed resecting the distended part of the sigmoid colon applying an end colostomy with a distal end closure was done. The diagnosis of Hirschsprung disease was confirmed histopathologically. The patient was started on oral antibiotics and carglumic acid 600 mg q12h for the state of hyperammonemia and the unavailability of sodium benzoate. After its administration the ammonia levels dropped from 302 μmol/L to a nadir of 46 μmol/L. Taking into consideration our case carglumic acid proved to be an effective ammonia scavenger in such cases.

CT-157 Another Rare Case of COVID-19 Vaccine Induced Acquired Hemophilia

Context: Acquired hemophilia A is an autoimmune bleeding disorder that results from autoantibodies against coagulation factor VIII. Failure to recognize AHA as a cause of bleeding results in delayed management. Objective: Case report of acquired hemophilia after receiving COVID-19 vaccines (Pfizer-BioNTech SARS-CoV-2 mRNA vaccine). Design and Patient Criteria: A case report of a lady who attended the haematology clinic at the University College London hospital. This included history taking, physical examination, full blood count, coagulation screen and factor assay, factor VIII inhibitor assay, immune workup, and CT scan. Main Outcome: We reported this 40-year-old lady with no previous medical history. She presented with massive vaginal bleeding and anemia which needed a blood transfusion. This coincided with her first dose of the Pfizer vaccine. Investigations showed high APTT at 45 sec, Factor VIII level at 0.3 IU/ml, Factor VIII Bethesda antibodies assay at 0.8 with normal other coagulation work up. Immune profile (ANA, Anti-dsDNA, C3, C4, and lupus workup) was negative and CT whole body showed no abnormalities. She was started on prednisolone 60 mg after which her bleeding improved and factor VIII level increased to 0.5 IU/ml. Once she started steroid withdrawal bleeding re-occurred and factor VIII level dropped to 0.21 IU/mL with APTT prolongation to 45 sec. Subsequently, she received 4 weeks of rituximab resulting in Factor VIII level normalization at 1.51 IU/ml, normal clotting screen and resolution of bleeding which has been sustained since November 2021. Conclusions: While thrombosis is a side effect of COVID-19 infection, bleeding can still happen in the setting of COVID-19 infection/vaccination. Till recently, only a few cases of acquired hemophilia have been reported after receiving mRNA-derived COVID-19 vaccines. Related Haematologic autoimmune disease may involve stimulation of auto-antibody production from preexisting B cells by triggering autoimmunity. It is crucial to raise awareness about this side effect that may be directly induced by the mRNA COVID-19 vaccine. We highly recommend screening for an antibody inhibitor with unexplained bleeding and/or isolated activated partial thromboplastin time prolongation following the COVID vaccine.

Life-threatening chlorpromazine-induced acquired haemophilia A in a patient with a cavernous malformation involving the medulla oblongata

IntroductionChlorpromazine is a commonly used drug in several medical conditions associated with a wide range of side effects. Few cases of hemostatic disorder have been reported in the literature. Case reportA 39-year-old man had previously been diagnosed with a cavernous malformation of the medulla oblongata. Chlorpromazine was started to treat persistent hiccups. Twenty days later, the patient presented hepatitis and a pruritic rash. Haemostasis tests revealed a prolonged partial thromboplastin time associated with isolated decrease of factor VIII level and anti-factor VIII antibodies. Magnetic resonance imaging revealed recent asymptomatic bleeding. Introduction of eptacog alfa and prednisone allowed clinical and biological improvement as well as a prolonged remission after 12 months of follow-up.

An international study on activated partial thromboplastin time prolongation. Part 2: Interpretative commenting

BackgroundProviding evidence-based interpretative comments (IC) is an integral task of clinical laboratory professionals. It may be of special relevance for coagulation testing, where pathological first-line tests could trigger more specialized tests. Our aim was to evaluate the quality of ICs provided to the physician in two samples with activated partial thromboplastin time (APTT) prolongation. Material and methodsTwo lyophilized plasma samples and their respective fictional clinical cases (case 1: heparin contamination and case 2: factor VIII deficiency) were sent to European laboratories for APTT and APTT mixing test measurement, and elaboration of ICs based on their results.The quality of ICs was evaluated in terms of analytical classification, laboratory interpretation, advice to physician, clarity, length and whether the clinical question was answered. ResultsA total of 214 laboratories were included. Classification of the analytical result was stated in 57 % of comments. Laboratory interpretation was found in 91 % of comments for case 1 and 83.3 % for case 2, among which 9.3 % and 6.5 % were considered wrong, respectively. Advice for the requesting physician was provided in 65.8 % of comments for case 1 and 61.2 % for case 2, among which 36 % and 4.7 % were considered wrong, respectively. More than 70 % of comments for both cases were evaluated as clear and of an adequate length. ConclusionA significant number of laboratories provide clear interpretations and helpful advice for the management of altered coagulation results. Nevertheless, the finding of several confusing and misleading comments highlights the need for recommendations on elaboration of interpretative comments.

An international study on activated partial thromboplastin time prolongation. Part 1: Analytical results

BackgroundUnexpected prolongation of first-line coagulation tests, including activated partial thromboplastin time (APTT), should trigger further work-up by performing mixing tests to elucidate the underlying cause, direct further specific testing and clarify their possible clinical impact. The aim of our study was to assess whether methodological diversity has any impact on the APTT mixing test results and their interpretation. Material and methodsTwo lyophilized plasma samples (case 1: heparin contamination [0.5 IU/mL]; case 2: factor VIII deficiency [0.13 IU/mL]) and their respective fictional clinical cases were sent to European laboratories for APTT measurement and performance of mixing tests.Participants were surveyed about the methodology (reagents, analytical platform, reference ranges), APTT results, mixing test conditions, their classification (normal, equivocal, prolonged) and categorization of the sample (factor deficiency, presence of inhibitor, anticoagulant, unknown). ResultsA total of 269 responses were included. For case 1, all participants reported a prolonged APTT, and 91% obtained no correction in the mixing test, without differences among reagents or analytical platforms. Only 15% of them selected the presence of an anticoagulant as the single cause for the prolongation.For case 2, 99% of participants reported a prolonged APTT, while some heterogeneity in the mixing test results was found. Eighty-six percent of participants selected factor deficiency as the cause for APTT prolongation. ConclusionsMost European laboratories obtained valid results for APTT and the subsequent mixing tests, despite using different methodologies. However, their classification could be improved. Therefore, more training and periodic evaluations are recommended to harmonize protocols and ensure proper result classification and categorization.

Tigecycline-Associated Coagulopathy: A Single-Center Retrospective Analysis

Introduction: The purpose of this study was to assess clinical characteristics and risk factors for tigecycline-associated prothrombin time (PT) and activated partial thromboplastin time (aPTT) prolongation. Methods: We performed a retrospective analysis on coagulation parameters before and during tigecycline treatment in 55 patients in our hospital with severe infections, mainly pneumonia caused by Acinetobacter baumannii. Patients were divided into different groups according to prolongation of PT and aPTT, and clinical features involved were explored. Univariate and multivariable binary logistic regression analyses were used to identify risk factors for tigecycline-associated PT and aPTT increase. Results: We found that PT values increased from 12.73 ± 1.87 to 13.86 ± 2.06 during the treatment compared with premedication (p < 0.001), and the aPTT level prolonged significantly from 33.63 ± 11.24 to 38.15 ± 11.81 (p < 0.001). The multivariate analyses identified 2 variables that were associated with tigecycline-induced PT prolongation: albumin level (p = 0.018) and weight-adjusted tigecycline dosage (p = 0.005). In addition, treatment duration was the only risk factor for tigecycline-induced aPTT prolongation (p = 0.043). Conclusion: Albumin level, weight-adjusted tigecycline dosage, treatment duration may serve as risk indicators for tigecycline-associated coagulation dysfunction. Physicians should be careful with coagulation disorder when prescribing tigecycline in clinical practice, especially in patients with risk factors.

Multisystem inflammatory syndrome in a neonate with severe hemophilia - a diagnostic challenge in COVID times: a case report

BackgroundMultisystem Inflammatory Syndrome in Neonates (MIS-N) can occur following antenatal COVID- 19 infection in the mother. Here we report a rare case of a neonate with Hemophilia A and MIS-N.Case presentationA 2-day-old baby presented with an intramuscular hematoma, neonatal seizures, and isolated activated partial thromboplastin time (APTT) prolongation. The neurosonogram showed a subdural hematoma. A diagnosis of Hemophilia A was made and was confirmed by factor 8 assay and genetic analysis. Supportive measures and Factor 8 replacement was initiated. A rising trend of inflammatory markers and an ongoing need for mechanical ventilation were noted. As there was a history of COVID-19 in the mother in the third trimester, MIS-N was diagnosed. The baby was treated with intravenous immunoglobulin (IVIG) and steroids, and there was an improvement in the clinical and laboratory markers. However, the baby developed seizures on day 16. There was an increase in the subdural hemorrhage and a further rise in inflammatory markers. A craniostomy and hematoma evacuation was done and the baby improved.ConclusionThe concurrent occurrence of hemophilia A with intracranial bleed, and MIS-N in a neonate is a diagnostic challenge. It is important to have a high index of suspicion to ensure timely diagnosis and treatment of MIS-N in this pandemic era.