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Chronic periprosthetic joint infection (PJI) is a devastating complication that requires an aggressive eradication protocol. Local antimicrobial delivery via dissolvable calcium sulfate (CaSO4) using small-sized beads (3–8 mm) has been utilized as an adjunctive treatment combined with implant exchange, radical debridement, and antimicrobial loaded acrylic spacers. The non-exothermic setting of CaSO4 theoretically allows for any antimicrobial agent to be used, so long as mixing methods provide a consistent fabrication within a reasonable set time. This study performed the first in vitro mixing study, in which various antimicrobial agents, used singularly and in combination, were mixed with a synthetic CaSO4 product to observe and document their interactions. The study was performed in a simulated operating room environment. We report a standard mix formula with set times, testing 22 different antimicrobial agents, combinations, and doses. For some antimicrobials and combinations, set times using the standard formula were either too fast or exceedingly slow. For these 14 antimicrobial agents and combinations, we were able to arrive at individualized mixing methods. We present all mixing formulas and set times. In all, we were able to establish mixing methods that incorporate all antimicrobial agents and combinations that we have seen utilized via surgeon-directed use.

OBJECTIVE To compare the efficacy of fresh frozen plasma (FFP) with cryopoor plasma (CPP) to treat vitamin K-dependent factor deficiency in a canine in vitro setting. DESIGN In vitro laboratory study. SETTING University veterinary medical teaching hospital. ANIMALS Seven units of FFP and 6 units of CPP from unique canine donors from the university veterinary blood bank. INTERVENTIONS Canine FFP was adsorbed by oral barium sulfate suspension to mimic vitamin K-dependent coagulopathy. A sequential mixing study was completed by adding FPP or CPP to the adsorbed plasma. Measurements of prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and factor activities of factors II, VII, and IX (FII, FVII, and FIX) were compared between the 2 treatment groups. MEASUREMENTS AND MAIN RESULTS When comparing the sequential addition of CPP or FPP to adsorbed plasma, the following had no statistical significance: PT (P = 0.94), aPTT (P = 0.66), FII (P = 0.05), and FIX (P = 0.90). There was a dose-dependent decrease with PT and aPTT and a dose-dependent increase with FII and FIX. In contrast, after the addition of either CPP or FFP, there was a significant difference between the treatment groups for the concentration of fibrinogen (P = 0.005) and activity of FVII (P = 0.044), with FFP resulting in a greater concentration of fibrinogen and CPP resulting in a greater concentration of FVII. Measurements of factor X (FX) were initially included in the study but were later excluded because FX appeared to be continually adsorbed even after the addition of CPP or FFP. CONCLUSIONS CPP partially corrected the coagulation times and concentration of vitamin K-dependent coagulation factors to the same degree as FFP. CPP, generally less expensive than FFP, may provide an alternative treatment option for vitamin K-dependent coagulopathies, although in vivo testing is needed.

Introduction: It is difficult to interpretate mixing study results (both screening & confirmatory) in presence of LAC. The main objective of this study is to define cut off values for ICA & % Correction which will reduce the no. of false positive & negative cases & will help in proper categorization of factor deficiency & inhibitors. This study also briefs about preanalytical errors & their correction Material and Methods: Rosner Index= × Cut offs ? 10 = Correction & ? 15 = Inhibitor Latest Sysmex CS-5100 auto-analyser was used to determine the Cut-offs. DRVVT mixing test ratio (Rosners index/ ICA) 1.15, % correction = 10, DRVVT Normalised ratio (NR) = 1.05. p value 15 is 91.1% sensitive for inhibitor diagnosis & it could not categorise, 8% of total cases into factor deficiency /inhibitor. Discussion: Rosners index (ICA) as a confirmatory test for LA is more sensitive than % correction & DRVVT NR. Chang’s % correction with a cut off value of >70% is 85% sensitive in diagnosing factor deficiency & a cut off value of Conclusion: It can be safely concluded that Rosner index is better than % correction, both as a screening test & confirmatory test, to differentiate factor deficiency from inhibitor. This study results are in agreement with CLSI guidelines & favours the sequential order screen-confirm- & then if required mixing study as in case of screen and confirm analysis is not clear-cut and/or when other causes of prolonged clotting times are known or suspected The draw back with the mixing studies is that weak LAC can be missed. Though in this study Nijmegen is better than Bethesda in terms of sensitivity & specificity as the later gives false positive results, other studies has to be taken into consideration which shows that both the Bethesda & Nijgmegen technique have low specificity at higher inhibitor titre. If actual quantitation of high titre activity is required, then it is more reliable to estimate empirically plasma dilution that gives 50%

Macrotroponin is a complex formed between endogenous cardiac troponin autoantibodies (cTnAABs) and circulating cardiac troponin (cTn). The potential effect of macrotroponin on current high sensitivity cTn assays has not been fully explored but has recently been identified as a major cause of discrepancy in cTn results between assays. In this study we investigated the effects of mixing troponin (cTn) standards to specimens with and without macrotroponin.Macrotroponin was identified in specimens by a recovery of cTnI 40% following protein A immunoglobulin depletion. Troponin standards containing cTn-IC and cTn-TIC complexes were mixed with serum samples, with (n = 20) and without (n = 10) the presence of macrotroponin. Specimens were tested for cTn before and after mixing by three commercially available high sensitivity cTn assays. Gel filtration chromatography was carried out on five specimens with macrotroponin and each fraction was analzyed by multiple cTn assays.Following mixing with cTn-TIC standard, all specimens with macrotroponin had a markedly reduced absolute increase in cTnI, indicating negative analytical interference due to macrotroponin. Following mixing with the cTn-IC standard, specimens with macrotroponin demonstrated highly variable changes in cTnI, suggesting significant heterogeneity in macrotroponin complex reactivity between individuals. When the ratio of change, calculated by dividing the absolute change between two cTn assays, was compared between specimens with and without macrotroponin, significant differences were observed (p 0.001). These findings were supported by variable migration of peak cTn activity on gel filtration chromatography.Macrotroponin leads to assay dependent analytical interference affecting current high sensitivity troponin I assays. Furthermore, endogenously occurring cTnAABs are conformationally specific and the analytical effects vary between assays and individuals.

Platelet-type von Willebrand disease (PT-VWD) is a rare autosomal dominant platelet bleeding disorder, with 55 patients reported worldwide so far, probably frequently misdiagnosed. Currently, there are no clear guidelines for the diagnosis and management of PT-VWD and this may contribute to misdiagnosis and thus to inappropriate treatment of these patients. This report provides expert opinion-based consensus recommendations for the standardized diagnostic and management approach to PT-VWD. Tests essential in the diagnostic workup are platelet count and size, ristocetin-induced platelet agglutination with mixing studies, and sequencing of platelet GP1BA gene. Platelet transfusions and von Willebrand factor-rich concentrates (if VWF is low) are the most effective treatments. This consensus may help to avoid misdiagnosis and guide appropriate management of patients with this disease.

Abnormal values for standard laboratory tests of coagulation are frequently reported in critically ill patients. Sepsis-associated coagulopathy with prolonged prothrombin time and thrombocytopenia is common among patients hospitalized in the intensive care unit (ICU). Isolated prolongation of activated partial thromboplastin time (aPTT) occurs less frequently in the ICU setting and has numerous causes. Moreover, there are several preanalytical factors that may impact on results obtained. Isolated prolongation of aPTT in the absence of clinically relevant bleeding is a common finding in patients in the ICU. The first step in the diagnostic process is exclusion of preanalytical error. Next, based on the clinical picture (normal haemostasis vs. bleeding tendency), the appropriate tests should be ordered, taking into account acquired and congenital causes. To establish a diagnosis in a timely fashion, the proposed practical diagnostic algorithm can be followed.

Background Major discrepancies between concentrations of serum total carbon dioxide (tCO2) obtained from chemistry analyzers and calculated bicarbonate from blood gas analyzers should prompt laboratory investigation. Here, we present a rare case of pseudohypobicarbonatemia unrelated to the common causes such as hypertriglyceridemia and hyperproteinemia, but was caused by a low concentration of paraproteins. Case A 75-year-old man with persistent fevers was found to have a low concentration of serum tCO2 ( Results Mixing studies revealed non-linearity of serum tCO2, suggesting the presence of interfering substances. Triglyceride concentrations were normal. Serum electrophoresis revealed a 0.4 mg/dl M-protein. The patient’s serum tCO2 concentrations were repeated on different chemistry analyzer platforms – including Siemens, Roche, and Abbott – which demonstrated that the interference was specific to the Siemens chemistry analyzer. Serum tCO2 was significantly elevated after ultrafiltration of paraprotein, which confirmed the root cause of pseudohypobicarbonatemia. Conclusion Laboratory professionals should be aware that spuriously low serum tCO2 concentrations may result from unique interfering substances, such as paraproteins, that are both patient- and chemistry analyzer-specific.

INTRODUCTION: An algorithmic approach, termed the prolonged clot time profile (PROCT), consisting of initial screening with prothrombin time (PT) and activated partial thromboplastin time (aPTT), reflexive mixing studies if indicated, and follow-up assays depending on initial testing results, offers an efficient approach to delineate the etiology of a prolonged PT/aPTT. Herein, we present the outcomes of the PROCT in the outpatient setting. METHODS: In this retrospective study, we reviewed medical records of consecutive outpatients who had prolonged PT and/or aPTT noted in the routine coagulation laboratory and who had PROCT ordered in our institutional Special Coagulation Laboratory between 2010 and 2017. RESULTS: One hundred and six patients, median age 55 years (IQR 30-67), met our study criteria. Twenty-nine patients had normal PT/aPTT, while 77 had persistent abnormalities and underwent reflexive testing. A prolonged PT, aPTT, or PT and aPTT was noted in 27 (35%), 27 (35%), and 23 (30%) respectively. Forty-nine (64%) had an acquired condition, 17 (22%) had a congenital condition, 7 (9%) had unclear etiology, and 4 (5%) were the result of laboratory artifact. The most common known cause of an isolated prolonged PT in our study was vitamin K deficiency in 8 (10%), the most common cause of an isolated prolonged aPTT was lupus anticoagulant in 4 (5%), and the most common cause of prolonged PT and aPTT was liver disease in 11 (14%). CONCLUSION: Prolonged PT/aPTT have a wide range of causes, including artifactual prolongation or abnormalities in secondary hemostasis due to both inherited and acquired conditions.

A previously healthy 11-year-old girl presented with bilateral orbital compartment syndrome secondary to retrobulbar hemorrhages requiring emergency cantholysis. Four days earlier she had sustained head trauma without symptoms until her acute presentation. A basic hematologic profile was remarkable for a prolonged partial thromboplastin time, which did not completely correct with a 1:1 mixing study. This result raised suspicion for the most common acquired deficiency of clot stability, acquired factor VIII deficiency (acquired hemophilia A). Low factor VIII levels and the presence of autoantibodies against autologous factor VIII were confirmed. The child was treated daily with fresh frozen plasma and showed marked improvement over the ensuing days and weeks.

The antiphospholipid syndrome (APS) is a thrombophilic condition characterised by thromboses and/or adverse pregnancy outcomes. International criteria for the diagnosis of APS require that certain laboratory and clinical criteria are met. Lupus anticoagulant (LA) testing using coagulation tests is an essential component. This review aims to provide a national guideline for LA testing in the South African context and intends to standardise testing, interpretation and reporting of results. Key aspects of the pre-analytical, analytical and post-analytical phases of testing are considered and highlighted. The full articles is available at https://doi.org/10.36303/JMLSTSA.2020.2.1.39

Mixing tests have long been a mainstay in the lupus anticoagulant (LA) testing armoury of screen, mix and confirm assays. If a sample with an elevated screening test does not evidence inhibition in the mixing test, the search for an LA is halted and a different diagnostic pathway embarked upon. Recent years have seen studies evidencing sometimes high frequencies of false-negative mixing tests with perhaps sinister implications for missed diagnoses and skewed patient management. Issues such as the dilution effect, between-reagent sensitivity and specificity differences, variability of normal pooled plasma (NPP) quality and suitability and interpretive inconsistencies all contribute to questioning the reliability of mixing tests and their pivotal place in the LA assay hierarchy. The advent of integrated testing, where phospholipid-dependence is demonstrated or excluded prior to any attempt to evidence inhibitory properties with a fallible analytical principle, provides an alternative path to LA detection. In the absence of other causes of elevated clotting times, LA assay screen and confirm discordance is sufficient to secure a laboratory diagnosis of the presence of an LA, leaving the mixing test in a supplementary yet valuable role when further diagnostic discrimination is required.

Basic coagulation tests, activated partial thromboplastin time (APTT), prothrombin time (PT) and the related international normalised ratio (INR), are performed frequently in hospital settings. From a laboratory perspective, unexpected abnormal results require further action; either informing the ordering clinician, or second line testing to determine the underlying cause. To streamline laboratory workflow, a new system of expert laboratory rules was implemented. The medical implications of this new laboratory system are evaluated here. The electronic ordering system was updated to mandate clinical information regarding the presence of an anticoagulant, or 'no anticoagulant'. When the PT or APTT were abnormal, and no anticoagulant was reported, second line testing was automatically performed. The second line tests performed were: mixing studies, fibrinogen and thrombin time. Any sample with a mixing study that did not completely correct, or fibrinogen1.0 g/L, or INR7.0, was flagged for clinical review by the laboratory haematology registrar. In a 17-month period there were 362,692 APTT, PT/INR and fibrinogen tests performed. Of these, 14,160 (3.9%) were abnormal with either no reported anticoagulant, or an unknown anticoagulant status. A total of 934 (0.3%) were referred for review by the haematology registrar. Three (0.001%) cases received altered medical management as a result of the haematology registrar review. In hospital settings, most abnormal coagulation studies are anticipated by the ordering clinician. Unexpected abnormal coagulation results of clinical significance are rare. Automated second line coagulation testing and medical review improves laboratory workflow without compromising patient safety.

In patients with autoimmune diseases, the simultaneous occurrence of lupus anticoagulant and blood coagulation factors inhibitors is infrequent and is associated with hemorrhagic events. In these cases, the initial approach requires a thorough interpretation of coagulation laboratory tests and mixing studies to reach a definitive diagnosis. We report the case of a patient with systemic lupus erythematosus and Sjogren’s syndrome who presented with hemorrhagic diathesis caused by circulating inhibitors against factors VIII and XI coexisting with lupus anticoagulant. The inhibitors eradication was made with rituximab, achieving good results.

OBJECTIVES To apply a simple method to validate testing for albumin, glucose, lactate dehydrogenase (LDH) and total protein (TP) in peritoneal, pleural, and cerebrospinal fluids (CSF) at a hospital in Liberia. METHODS Serum and body fluid specimens were mixed to create 100% serum and 25%, 50%, 75%, and 100% fluid tubes, which were tested on a Biotecnica BT3500. Differences less than 10% between calculated and measured concentrations were considered acceptable. RESULTS The means (confidence intervals) of the percent differences were: albumin/peritoneal 12.8 (6.0-19.7), albumin/pleural 2.8 (1.3-4.2), albumin/CSF 4.8 (2.2-7.5), glucose/peritoneal 4.0 (1.9-6.0), glucose/pleural 4.4 (3.1-5.7), glucose/CSF 2.9 (1.8-4.0), LDH/peritoneal 9.5 (6.3-12.7), LDH/pleural 9.5 (5.4-13.6), LDH/CSF 9.2 (5.2-13.3), TP/peritoneal 7.6 (3.8-11.4), TP/pleural 3.8 (1.5-6.2), and TP/CSF 4.5 (1.0-8.1). CONCLUSIONS All mean differences except for one were less than 10%, allowing for the adoption of clinical testing. The mixing study is a low-cost method for quality-assured testing that can be performed by resource-limited laboratories.

Factor V deficiency is a rare bleeding disorder, which may be due to acquired inhibitors or biallelic mutations. Factor V deficiency due to homozygous or compound heterozygous mutation (also known as Owren's disease or parahemophilia) has an estimated prevalence of one in one million people. A 22-year-old female was admitted for evaluation of longstanding menorrhagia. Anatomic abnormalities were excluded, and prolonged prothrombin time (PT) and partial thromboplastin time (PTT) were identified. Mixing studies followed by specific factor assays and genetic testing enable identification of factor V deficiency, for which fresh frozen plasma (FFP) or factor V concentrates are therapeutic. Specific clotting factor assay followed by mixing studies and genetic studies is essential for the diagnosis of congenital factor V deficiency. Deranged PT and activated partial thromboplastin time (APTT) with normal factor I level must be evaluated for the disorder of clotting factors and must be managed by FFP administration or plasma-derived factor V concentrate wherever available.

Objectives Macrotroponin is due to cardiac troponin (cTn) binding to endogenous cTn autoantibodies. While previous studies showed a high incidence of macrotroponin affecting cTnI assays, reports of macrotroponin T, particularly without cTnI reactivity, have been rare. Although the clinical significance of macrotroponin is not fully understood, macroenzymes and complexes are recognised to cause confusion in interpretation of laboratory results. The potential for adverse clinical consequences due to misinterpretation of affected results is very high. Methods We describe four cases of macrotroponin T with persistently low high sensitivity cTnT (hs-cTnT) by the 9 min compared to the 18 min variant of the assay. Three cases were serendipitously identified due to the use of a lot number of Roche hs-cTnT affected by non-reproducible results, necessitating measurement of cTnT in duplicate. We identified and characterised these macrotroponin specimens by immunoglobulin depletion (Protein A and PEG precipitation), mixing studies with EDTA and recombinant cTnT. Results In cases of macro-cTnT, a lower result occurred on the hs-cTnT using the 9 min compared to 18 min variant assay (ratio of 9–18 min hs-cTnT Conclusions We identified several cases of macro-cTnT and described associated clinical and biochemical features.

International audience; We introduce an original chemical reaction between two transparent reactant solutions (fluorescin and potassium ferricyanide), producing a fluorescent product in water (fluorescein). The reaction has a tunable kinetics, allowing the quantitative investigation of the interplay between molecular diffusion and reaction kinetics in various reactant field topologies. We document the chemical reaction kinetics and its sensitivity to ambient pH, temperature, reactants concentrations, etc., and we implement it in two simple reactant-contacting geometries in a Hele-Shaw cell. The resulting reaction-diffusion zones and product formation rates exhibit either the reaction-controlled or diffusion-controlled regimes, as well as a new "diffusio-chemical" regime which we show to be inherent to the early time transient dynamics of any bimolecular reaction between initially segregated reactants. The potential interest of this reaction, opening prospects for the study of reactive mixing, is underlined.

Background: Lupus anticoagulant (LA) owns procoagulant properties in vivo and prolongs phospholipid-dependent clotting times in vitro. The prolonged in vitro clotting time can be misinterpreted as a bleeding disorder. In some cases, it is necessary to differentiate LA-associated in vitro changes from in vivo coagulation factor deficiency. In this case, we used different laboratory testing in a patient with ischemic stroke and reduced prothrombin time (PT) to identify an in-vitro effect of LA excluding an in-vivo bleeding disorder. Methods: The activity of various coagulation factors was evaluated both with recombinant thromboplastin Innovin (Siemens Healthcare) and reagent tissue extracted thromboplastin Thromborel® (Siemens Healthcare). Moreover, a 1:1 plasma mixing test with standard plasma was performed. In order to exclude the interaction of tromboplastin and LA thromboplastin, an independent global coagulation test, thromboelastography, was used. Diluted-Russel-Viper-Venom (dRVVT) assay was applied to detect the presence of LA detection. Results: The activity of several coagulation factors measured with recombinant thromboplastin Innovin (Siemens Healthcare) showed a reduced activity of the following coagulation factors: Factor V (20.9%), Factor VII (23.8%), Factor X (19.7%) and international normalized ratio (INR) of 2.33. Re-assessment of the factor's activity with another reagent tissue extracted thromboplastin Thromborel® (Siemens Healthcare) showed a normalization of INR and factor's activity in comparison to thromboplastin reagent Innovin®: Factor V (77%), Factor VII (45.4%), Factor X (64.2%), and INR of 1.28. A plasma mixing study with 1:1 standard plasma revealed reduced (

Acquired hemophilia A (AHA) occurs rarely in children. We report 2 cases of adolescent females with AHA. The first case underwent bone marrow aspiration/biopsy during workup, which was complicated by bleeding. Bleeding resolved after initiation of therapy with cyclophosphamide and glucocorticoid, but despite the addition of rituximab, she did not achieve complete remission until treatment with intravenous immunoglobulin. In the second case, we observed that a mixing study without incubation will not detect an acquired factor VIII inhibitor, but further workup based on suspicion for AHA led to the correct diagnosis. Both had significant medication toxicity which required treatment modification.

Prekallikrein (PK) deficiency is extremely rare, and manifestations are not well characterized due to a small number of cases reported and the lack of scientific clarity about its role in clot formation in vivo. Here, we report a case of a 64-year-old male, with no known history of abnormal bleeding, who scheduled to undergo deep brain stimulator placement for control of his Parkinson's disease. During pre-procedure testing, activated partial thromboplastin time (PTT) was found to be prolonged at 146 seconds. Mixing studies were suggestive of a coagulation factor deficiency. His PTT characteristically became shorter with prolonged incubation, providing a clue at testing for PK levels, which were found to be severely low. He, subsequently, underwent surgery without any complications. Our case further highlights the clinical pearls for diagnosis and further endorses that these patients can safely undergo surgical procedures without the need for plasma transfusions or factor concentrate usage.

Background Due to the narrow therapeutic range of digoxin , determining serum/plasma digoxin concentrations is critical for assessing patients with congestive heart failure , atrial fibrillation , and certain types of arrhythmias. However, digoxin quantification by competitive immunoassays is susceptible to interferences that may alter the accuracy of its measurement in patient plasma. This study aimed to characterize the extent of bilirubin interference in three commonly used digoxin immunoassays. Methods Digoxin concentrations were compared using the Beckman Coulter® Unicel DxI 800, the Vitros® 4600, and the Roche Cobas® 8000 in neat or digoxin-spiked icteric and non-icetric plasma samples. A mixing study was performed to demonstrate how digoxin quantification is affected by bilirubin. An equation was derived that predicts the response of the DxI 800, given known bilirubin and digoxin concentrations. Results The DxI reported detectable concentrations of digoxin in high bilirubin samples with no added digoxin, while the Vitros® 4600 and Cobas® 8000 gave virtually undetectable results. Spiking digoxin into samples with elevated bilirubin concentrations resulted in a higher percent recovery for the DxI 800 when compared to the other two platforms. The mixing study also revealed an increase in the percent recovery in the DxI 800, while the Vitros® 4600 and Cobas® 8000 were comparable to the expected concentration of digoxin. Conclusions The DxI 800 is most prone to interference by bilirubin, while the Vitros® 4600 and Cobas® 8000 are relatively unaffected. Icteric samples should be interpreted with caution if digoxin quantification is needed, especially on the DxI 800 assay.

Painless bleeding in a patient presenting from the community with elevated coagulation studies rarely makes the physicians suspect superwarfarin or rodenticide poisoning. Although a significant number of superwarfarin exposure cases are diagnosed every year, we believe there appears to be delay in diagnosis and confusion in determining what is the ideal way to treat and monitor these patients during the management. This is the first thorough literature review of all the reported cases of superwarfarin poisoning which also studied the clinical presentation, management and follow-up patterns. We present a 70-year-old man who presented to the emergency room with epistaxis, melena, cola-colored urine with elevated prothrombin time (PT), activated partial thromboplastin time (aPTT) and international normalized ratio (INR). Mixing studies showed complete correction of coagulopathy indicative of factor deficiency. Additional history revealed that the patient had arguments with family member at home and made us suspect superwarfarin exposure. Qualitative brodifacoum testing was positive and was managed with fresh frozen plasma and high doses of vitamin K1 (phytomenadione) with serial monitoring of INR and clinical symptoms. Superwarfarin poisoning should be considered in the differential diagnosis of a patient who presents with above clinical and laboratory profile especially in the absence of any history of coagulopathy or anticoagulant use. We want to raise public and especially physician awareness that history taking, early diagnosis and managing in right clinical setting play a significant role in survival of these patients.

Most fibrinogen replacement strategies focus on quantitative deficiencies. A thrombin time (TT) mixing study helped to assess qualitative defects caused by dysfibrinogens. Plasma samples were collected from non-anticoagulated subjects (n=6) meeting laboratory criteria for suspected dysfibrinogenaemia (TT > 22 s; fibrinogen activity

Bleeding during and after surgery ranges from trivial to fatal. Bleeding is in part determined by the patient's coagulation status. The UK National Institute for Health and Care Excellence recommends a pre-operative clotting test for patients with a history of abnormal bleeding. Anaesthetists are familiar with the prothrombin time assay, used to monitor warfarin effect, but anaesthetists may be less familiar with the activated partial thromboplastin time (APTT), which tests the function of the 'intrinsic' clotting pathway. The activated partial thromboplastin time may be prolonged due to contamination, anticoagulant therapy, clotting factor deficiencies, lupus anticoagulant or acquired inhibitors of specific clotting factors. A prolonged activated partial thromboplastin time should lead to: further testing to exclude heparin contamination or therapy, mixing studies to identify factor deficiencies and if necessary dynamic studies, such as the dilute Russell's viper venom time and the Actin FS-activated partial thromboplastin time, to identify direct factor inhibitors. These tests identify abnormalities and their implications for bleeding, helping anaesthetists and haematologists to manage haemostasis for individual patients.

An 80-year-old man with no personal or family history of bleeding, presented to hospital with extensive haematomas and skin bruising after using doxycycline. His basic lab workup was concerning for a coagulopathy with an elevated activated partial thromboplastin time and significant anaemia. Mixing studies and other factor levels were tested that led to the diagnosis of acquired haemophilia A with low factor VIII levels and high factor VIII antibodies. He was started on steroids, but his haemoglobin level continued to drop. Later, during his treatment, he was given multiple therapeutic agents, including cyclophosphamide, rituximab and recombinant factor VII (NovoSeven-R). Gradually factor VIII levels increased and haemoglobin stabilised. The hospital course was complicated by COVID-19 pneumonia leading to acute respiratory distress syndrome; the patient eventually expired due to respiratory failure.

Lupus anticoagulant, also known as lupus antibody, is generally associated with thrombosis rather than bleeding events. Lupus anticoagulant-hypoprothrombinemia syndrome in children is rather rare but can lead to mild to life-threatening bleeding. Here, we report 3 cases of lupus anticoagulant-hypoprothrombinemia syndrome associated with systemic lupus erythematosus. They initially presented with mucocutaneous bleedings, and subsequently developed other symptoms fulfilling the laboratory criteria for systemic lupus erythematosus. Case 2 and 3 had significant epistaxis and intracerebral hemorrhage responded to systemic corticosteroid along with fresh frozen plasma. Three cases demonstrated acquired hypoprothrombinemia with no correction of mixing studies. Case 1 had low factor X level, which has never been reported previously. In all 3 cases, their coagulogram returned to normal level after corticosteroid treatment.