ABSTRACT
Introduction/Background: Primary bone marrow oedema syndrome is an elusive and less well-defined entity. Whether Rheumatologists should consider it as a stand alone diagnosis, is debatable. It possibly would be best described as an MRI feature which could be a finding in a number of diseases which would include the initial phases of Osteonecrosis of the bone, Rheumatoid Arthritis, Spondyloarthritis, Enthesitis related, Post traumatic, OA, Infections and Cancers. The treatment options become constricted due to the paucity of evidence. Rheumatologists need to consider this as an area of unmet need with development of consensus classification criteria and treatment approaches. Description/Method: 27-year-old male, Height 174 cms Weight 90 Kgs BMI 29 Kg/m2, became symptomatic in Jan 2022 with complains of pain in the both hip joints & groin regions, pain became excruciating and he became bed-bound, with early morning stiffness lasting approximately 45 mins. Had received steroids for COVID infection in August 2020. Investigations Hb 13.5gm/dl TLC 7000/mm3 Platelet 400 x 103/mm3 Sr Bil 0.8mg/dl AST 16 IU/L. ALT 24 IU/L Sr Creatininine 1.1mg/dl Blood Sugar Levels, Fasting 89 mg/dl Post Prandial 102 mg/dl ESR 10mm in 1st hour by Wintrobes method CRP Quantitative 29.38mg/L HLA B27 by PCR Negative, RF Negative, ACCP Negative Serum, IgG, Beta2 Glycoprotein 1.44 SGU Serum, IgM, Beta2 Glycoprotein 3.44 SGU Serum, IgG, Cardiolipin antibody 8.4 GPL Serum, IgG, Cardiolipin antibody 17.45 GPL Lupus anticoagulant by DRVVT Negative Sr Cholesterol 211mg/dl HDL 29 mg/dl LDL 156mg/dl TGs 130 mg/dl MRI Hips & SI joints Transient bone marrow oedema/osteopenia of bilateral hip. PET CT Increased metabolic activity in both hip joints Bone Scan (99mTcMDP) Increased vascularity in perfusion phase, increased accumulation in soft tissue in blood pool phase and increased uptake in bilateral Hip joints in skeletal phase scan, suggestive of CRPS Type-I. Management Was initially managed with Tab Etoricoxib 90mg BD, also started on Tab Sulphaslazine and Tab Methotrexate. However, when he had no symptomatic relief he was administered Inj Infliximab on 12 May 2022 and a second dose on 9 June 2022. He had excellent pain relief after the 1st dose, however after 10 days of the administration, he again began experiencing pain especially after walking. He also had pain in the knees on this occasion. He was also administered Inj Zoledronic 4mg on 23 May 2022. He is at present not requiring any NSAIDs over the last 1 month. Discussion/Results: The patient having presented with excruciating and debilitating pain was worked up and evaluation revealed features of bone marrow oedema on MRI which was corroborated with bone scan and PET CT imaging. The acute phase reactant CRP was also significantly elevated. The patient also gave history of early morning stiffness lasting approximately 45 mins. Hence an underlying Inflammatory process such as Spondyloarthritis(Peripheral) with enthesitis was considered. The confounding factors were the pain which worsened on mobilization, HLA B27 negative status, Rheumatoid Factor and ACCP negative status and past history of having received IV Corticosteroids for COVID infection in August 2020. In view of the debilitating pain and aworking diagnosis of Spondyloarthritis, hewas started onNSAIDs alongwith rest, initially, followed by conventional synthetic disease modifying agents in Rheumatic disease followed by biologic synthetic diseasemodifying agent - Inj Infliximab. The thought process was to avoid prolonged NSAID use to prevent the associated side effects. However, since Avascular Necrosis of the Femoral head is a very likely possibility, the patient is planned to be kept under close follow up. Key learning points/Conclusion: Collaborative efforts between the Departments of Nuclear Medicine, Radiology, Orthopaedics and Rheumatology are crucial in the early detection and approach to cases of Bone Marrow oedema. Avascular necrosis of head of Femur is a far more common entity and must be kept in ind even when a diagnosis of Bone Marrow oedema syndrome is being entertained. Diagnosis of Bone Marrow oedema syndrome must be entertained only as a diagnosis of exclusion. Continued follow up and regular imaging must be pursued rigorously in patients diagnosed with Bone Marrow oedema syndromes. There is a requirement to document acute phase reactants such as CRP and ESR in patients diagnosed with Avascular necrosis of bone as this data could help us differentiate AVN from Primary Bone marrow oedema in the early stages.
ABSTRACT
Introduction: Acquired hemophilia A (AHA) is a rare hemorrhagic disease in nonhemophiliacs (1 case/106 persons per year) due to autoantibodies/inhibitors against factor VIII. The disease occurs more often in the elderly, it is usually idiopathic and it causes sudden skin and mucosal bleeding. The aim of this study was to describe a case of AHA, diagnosed during hospitalization for COVID-19. Method(s): A female patient, 87 years old was hospitalized for COVID-19. She had no personal or family history of spontaneous bleeding and was not under anticoagulant therapy. Routine coagulation parameters, mixing test-aPTT and activity of coagulation factors were performed in ACL-TOP 750 (IL). Result(s): The first bleeding episode happened two months ago when the patient underwent coronary angiography and started bleeding mainly at the catheterization point (left radial artery). Three hospitalizations followed due to extensive ecchymoses and recurrent bleeding episodes at multiple sites of venipuncture, treated with hemostatic suturing and transfusions. The patient was subsequently admitted to our hospital due to COVID-19 infection and anemia. She presented with an isolated prolongation of activated partial thromboplastin time (aPTT) (>60) since the day of her first admission. In our hospital, a mixing-test of aPTT was performed: aPTTmix-direct = 40 [Rosner-Index = 11.45% (< 12% = correction)] aPTTmix-after two hours of incubation at 37degreeC = 62.5 [(Rosner-Index = 36.45% (>15% = no correction)] Therefore, the probable presence of a coagulation factor inhibitor was indicated. No lupus anticoagulant was detected (DRVVT-TR = 0.9). A reduced activity of FVIII = 1.9% (m.p.= 50-150%) was found and she was immediately treated with prednisolone, with positive clinical response, cessation of bleeding episodes and normalization of Hct and aPTT. Conclusion(s): AHA is the most common type of acquired hemophilia. An isolated prolongation of aPTT is usually due to anticoagulants mainly heparin. If not, it may indicate a clotting-factor deficiency or the presence of an inhibitor, that is either specific (e.g. antibody to factor VIII/AHA) or nonspecific (e.g. lupus anticoagulant). The mixing-test aPTT should be routinely used in these cases to detect AHA, a rare disease usually underdiagnosed that can be fatal without early recognition and appropriate management.
ABSTRACT
Introduction: Thrombophilia is a co-morbidity in the general population with a prevalence of 5%. However, it is not known whether it affects severity of COVID-19. It may be possible that undiagnosed thrombophilia exaggerates an already prothrombotic state in COVID- 19 patients and hence, results in severe disease. Aims & Objectives: To study the association of underlying thrombophilia with severity of COVID-19 in post COVID patients after a minimum of 6 weeks of recovery. Material(s) and Method(s): Eighty RT-PCR confirmed adult covid patients (40 severe,40 non-severe) post 6 weeks of recovery were included. The venous blood in EDTA and citrate vials was tested for complete blood counts and coagulation parameters such as Prothrombin time, activated partial prothrombin time, Lupus anticoagulant by dRVVT, Antithrombin-III, Protein C and S). Result(s): 6/40 patients had Protein C deficiency in severe category and none in non severe. 7/40 patients had Protein S deficiency in severe category and 1 patient was deficiant in non-severe group. Conclusion(s): Thrombophilia was detected significantly in patients with severe COVID even after 6 weeks of recovery, indicating that undetected underlying thrombophilia could be a factor affecting disease severity. The common abnormalities detected were Protein C & S deficiency. This is a novel finding which needs to be explored further with extensive thrombophilia profiles. The influence of underlying thrombophilia in patients who succumbed to the disease is not known and cannot be known retrospectively. However, the extrapolation of this study suggests that thrombophilia may be an important influence on severity and mortality. (Table Presented).
ABSTRACT
Background: Thrombosis is a frequent and severe complication in COVID-19 patients admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and is frequently observed in COVID-19 patients. Whether LA is associated with thrombosis in patients with severe COVID-19 is currently unclear. Aim(s): To investigate if LA is associated with thrombosis in critically ill COVID-19 patients. Method(s): The presence of LA and other antiphospholipid antibodies was assessed in COVID-19 patients admitted to the ICU. Informed consent was obtained by an opt-out approach and the study was approved by the local medical ethical committee. LA was determined with dilute Russell's Viper Venom Time (dRVVT) and LA-sensitive Activated Partial Thromboplastin Time (aPTT) reagents. Statistical analysis to study the association of LA and other antiphospholipid antibodies with thrombosis occurrence was performed using logistic regression. Result(s): Out of 169 COVID-19 patients, 116 (69%) tested positive for at least one antiphospholipid antibody upon admission to the ICU. Forty (24%) patients tested positive for LA;of whom 29 (17%) tested positive with a dRVVT, 19 (11%) tested positive with an LA-sensitive aPTT and eight (5%) tested positive on both tests. Fifty-eight (34%) patients developed thrombosis after ICU admission. The odds ratio (OR) for thrombosis in patients with LA based on a dRVVT was 2.4 (95%-CI: 1.1-5.4), which increased to 5.1 (95%-CI: 1.7-15.4) in patients on or below the median age of this study population (64 years). LA-positivity based on a dRVVT or LA-sensitive aPTT was only associated with thrombosis in patients younger than 65 years (OR: 4.2, 95%-CI: 1.5-11.7). Conclusion(s): LA on admission is strongly associated with thrombosis in critically ill COVID-19 patients, especially in patients <65 years of age.
ABSTRACT
Background: Argatroban is a direct thrombin inhibitor licenced in the UK and USA for treatment of Heparin Induced Thrombocytopenia and has been utilised as alternative anticoagulation for critically ill COVID-19 patients. Interferences in specialised haemostasis assays may be clinically important when bridging anticoagulant regimens or investigating thrombotic and bleeding complications common in critically ill patients. Aim(s): * Assess effect of Argatroban on specialised haemostasis assays * Assess effectiveness of DOAC-Remove (DR) in removing Argatroban interference Methods: Argatroban calibration plasma, spanning concentrations of 0 mug/ml-2.08 mug/ml, was tested for Antithrombin (IIa activator), Factors IX, and XI, and dilute Russel's viper venom time (dRVVT) to assess Argatroban interference. Samples were treated with DOAC-Remove and re-run for these assays. A p value of <0.05 was used to assess significance using paired t-tests Results: * Antithrombin results were significantly and linearly increased by increasing Argatroban concentrations (R -0.99). * Factor IX and XI concentrations were significantly decreased by increasing Argatroban concentrations from 83.4 IU/dl at 0 mug/ml to 3.79 IU/ dL at 2.07 mug/ml Argatroban * dRVVT screen results were significantly increased by increasing Argatroban concentrations (DRVVT ratio 1.07 (no Argatroban) to 3.79 at 2.07 ng/ml Argatroban) * Pre-treatment of samples with DOAC-Remove completely removes Argatroban interference to baseline. Conclusion(s): Argatroban has significant effects on specialist haemostasis assays. Antithrombin overestimation was observed when IIa activator is used, a Xa activator should be considered in such patients. dRVVT screen ratios were significantly increased, which could lead to false positive Lupus anticoagulant results. Factors IX and XI results were significantly decreased. Similar results have been published for direct oral anticoagulants with the need for pre-analytical screening, where anticoagulant status is unknown, becoming more important. For Argatroban, dilute thrombin time can be used as a pre-analytical screening tool. (Table Presented).
ABSTRACT
Background: Hypercoagulability has been established in COVID-19 and has been linked to thrombotic risk. The existence of an antiphospholipid (aPL) syndrome in COVID-19 remains controversial. Aim(s): Determine if markers of aPL syndrome are elevated in COVID-19 and associated with hypercoagulability and in-hospital clinical events. Method(s): Blood, urine, clinical data, and outcomes were analyzed in patients hospitalized with COVID-19 (n = 100) enrolled in the IRB approved TARGET-COVID study and in healthy subjects (n = 131). aPL syndrome was assessed using using lupus anticoagulant assays (dRVVT and Hex LA, Precision BioLogic Inc.);aPL antibody (APA) profiling (IgA,IgM,IgG) against aB2GP1, anticardiolipin (aCL), and anti-phosphotidyl serine (aPS) assays (Corgenix). Hypercoagulability, and coagulation markers (D-Dimer, Factor-V, VIII, XII, and Prekalikrein) were assessed using thromboelastography (TEG-6s), ELISA, and standard coagulation assays, respectively. Result(s): Mean age was 59 +/- 19 years;predominately African American (65%), with a high prevalence of hypertension (74%), obesity (53%), and diabetes (45%). LA positivity was observed in 2%;and 32%, 23%, and 9% by aB2GP1, aCL, and aPS antibody testing, respectively (Figure 1). Hypercoagulability defined by platelet-fibrin clot strength (MA >= 68 mm) was observed in 62% of the total group and was not associated with LA or APA positivity. Patients had lower FV, FXII, PK activity vs. healthy subjects (p < 0.05 for all). D-dimer was higher in patients with aPL's vs. negative patients (p = 0.03) but was not associated with thrombotic events (21% vs. 16%). Patients with positive aPS antibodies had higher mortality than aPS negative, and aCL positive, and aB2GP1 positive patients (44% vs. 18%, 10%, 7%;p< 0.05) respectively. Conclusion(s): Based on LA assay, aPL syndrome is infrequent in COVID-19. However, there is a high prevalence of aPL antibodies that correlate with D-dimer with the greatest prevalence observed for aB2GP1. aPS positivity correlated with mortality and deserves further investigation as a biomarker of poor outcomes. (Figure Presented).
ABSTRACT
Background: Coronavirus 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with severe hypercoagulable conditions and complex venous thrombosis is common. Several recent studies have reported elevated aPTT in COVID-19 patients with a thrombotic tendency, suggesting that the test results may be due to the presence of lupus anticoagulant (LA). LA, one of the antiphospholipid antibodies, is included in the diagnostic criteria for antiphospholipid syndrome (APS), and these syndromes are characterized by a tendency to thrombosis, so it is important to ascertain the meaning of LA in SARS-COV-2 infection. Here, we would like to investigate the changes in LA and the characteristics of coagulation-related factors in COVID-19 patients who have undergone LA testing. Methods: From March 2020 to June 2021, we conducted a medical record review of clinical information and laboratory data for COVID-19 patients at our hospital. Among the 140 confirmed patients, 110 patients who underwent lupus anticoagulant testing were included in the analysis. We also performed a subgroup analysis of COVID-19 patients who were regularly screened for LA. Results: Most of the patients in our study were mild, with 95 survivors except for the deaths of 15 patients. Lupus anticoagulant was identified in 71.6% of survivors and 40.0% of deaths. In the LA confirmatory test of survivors, DRVVT positive 98.5% and SCT positive 5.9% were found (Fig 1). When comparing coagulation parameters according to LA results in survivors, aPTT, CRP, and fibrinogen were found to be statistically significant (all P < 0.05). LA-positive patients had higher aPTT, CRP, and fibrinogen, and D-dimer was no different from LA-negative patients (Table 1). Of the 67 LA-positive patients, 25 patients did not follow up, and 12 patients were unable to clearly determine the duration of the negative transition. Among the 30 patients who underwent a follow-up LA test, short-term regular follow-up of LA testing was performed on patients from March 2021 to June 2021, and additional subgroup analysis was performed on these patients. All patients were confirmed to be DRVVT positive and had no other anti-phospholipid syndrome (APS)-related antibodies, such as anti-cardiolipin antibodies or anti-beta-2-gylcoprotein. LA disappeared rapidly within 4 weeks in all patients (range: 2-24 days). As the LA test result converted from positive to negative, aPTT decreased with a statistically significant difference (P=0.003, Fig 2). Conclusions: As previously reported, LA was found in a high proportion of COVID-19 patients. This is the first study to confirm that the proportion of LA positivity (71.6%) is high in Korean COVID-19 patients. Most of the LA positivity disappeared within 4 weeks instead of 12 weeks. The association between LA and thrombotic tendency in COVID-19 patients appears to be low. Presumably, the transient appearance of LA, which is rapidly disappearance in survivors at a high rate, may indicate that other autoantibodies due to the activation of the immune response were detected in the LA test, can be considered as a good indicator of prognosis. It is only necessary to note that there is no delay in anticoagulant treatment due to aPTT prolongation in the early stage due to LA. In summary, the clinical significance of high LA positive rates and rapid negative transitions in COVID-19 patients is currently unknown but needs confirmation. [Formula presented] Disclosures: No relevant conflicts of interest to declare.