BACKGROUND: Vitamin K (VK) deficiency (VKD) impairs γ-carboxylation of VK-dependent coagulation factors (VKDF), resulting in higher factor II (FII) levels measured by Ecarin (FIIE) reagents (that convert des-γ-carboxylated FII to meizothrombin) than by prothrombin time (FII) reagents.
OBJECTIVE: To evaluate FII/FIIE abnormalities among patients assessed for coagulopathies and identify findings predictive of coagulopathy improvement after VK.
METHODS: We retrospectively assessed consecutive cases between 2002-2021 with FII/FIIE tests and the sensitivity and specificity of FII/FIIE ratios and FIIE-FII differences for VKD defined as INR correction/improvement ≥0.5 after VK.
RESULTS: 292 patients (males 58.2%; adults 85.6%; median age 73 years) were evaluated (84.2% hospitalized, 48.3% in intensive care; 71.6% with active liver disease; 28% deceased at discharge) and 25-38% had FII/FIIE findings suggestive of VKD. Among 170 patients assessed for response to VK, FII/FIIE ratios ≤0.84-0.91 and FIIE-FII differences >0.04 U/mL had similar modest sensitivity (47.7-69.3%) and modest to good specificity (67.1-91.5%) for VKD. FII/FIIE ratios <0.86 suggestive of VKD (sensitivity: 47.7%; specificity: 90.2%) were more common in patients deficient in only VKDF (p=0.0001), but were detected in 16% with non-VKDF deficiencies. Low FIIE was commonly associated with active liver disease (p=0.0002). Patients with and without probable VKD (based on FII/FIIE ratios <0.86), had similar mortality, bleeding and rates of prothrombin complex concentrate and red cell transfusions (p≥0.78), but fewer with probable VKD received plasma and fibrinogen replacement (p≤0.024).
CONCLUSIONS: FII/FIIE comparison aids the diagnosis of VKD and predicts clinical responses to VK treatment among patients with coagulopathies.

Data on the pathophysiological mechanisms of hemostatic alterations in the thrombotic events that occur during Ramadan intermittent fasting (RIF), particularly in the natural coagulation inhibitors, are very limited. Thus, our objective was to evaluate the effect of RIF on the natural anticoagulants level, antithrombin, protein C, and total and free protein S (PS) in healthy participants. Participants were divided into two groups. Group I consisted of 29 healthy fasting participants whose blood samples were taken after 20 days of fasting. Group II included 40 healthy non-fasting participants whose blood samples were taken 2-4 weeks before the month of Ramadan. Coagulation screening tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and plasma fibrinogen level, natural anticoagulants; antithrombin, protein C, free and total PS and C4 binding protein (C4BP) levels were evaluated in the two groups. High levels of total and free PS without change in antithrombin, protein C, and C4BP levels were noted in the fasting group as compared with non-fasting ones (p < 0.05). PT and APTT showed no difference between the two groups. However, the fibrinogen level was higher in the fasting group. In conclusion, RIF was found to be associated with improved anticoagulant activity in healthy participants, which may provide temporal physiological protection against the development of thrombosis in healthy fasting people.

The direct-acting oral anticoagulant dabigatran etexilate (DE) targets thrombin and is used widely to prevent thromboembolism. A 79-year-old man was admitted to the Emergency Department due to anuria for 2 days. An urgent laboratory examination revealed a serum creatinine concentration of 888 µmol/L. He was diagnosed with acute exacerbation of chronic renal insufficiency. During continuous renal replacement therapy (CRRT), the coagulation test showed a severe reduction in the fibrinogen level as well as a significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). The patient had been taking DE (110 mg twice daily) for a long time and had not suspended the medication or reduced the dose during the worsening of anuria. Therefore, it should be evaluated before considering plasma replacement therapy for the patient, whether the abnormal coagulation parameters were induced by interference of excessive DE. Tentatively, we used activated charcoal to treat the plasma and then retested the fibrinogen, PT, and APTT. Results showed that the coagulation indices nearly returned to normal. The present case indicated that activated charcoal could adsorb DE in plasma effectively and eliminate its interference with coagulation test results, thereby providing support for clinical diagnosis and treatment.

With the development of modern medical standards, autoimmune diseases and their associated successive osteoporosis have received increasing attention in recent years. Patients with autoimmune diseases, due to the characteristics of the disease and the prolonged use of glucocorticoid hormone therapy, may affect the bone formation and bone absorption of the patient, followed by severe successive osteoporosis, thereby increasing the risk of osteoporotic vertebral fractures. Vertebral compression fractures of the spine are common fracture types in patients with osteoporotic fractures. Osteoporosis is a common complication after glucocorticoid therapy in patients with autoimmune diseases. Percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) are minimally invasive operation and are commonly used surgical methods for the treatment of osteoporotic vertebral compression fractures. However, due to the operation of spinal puncture during the operation, there are serious surgical risks such as bone cement leakage, spinal epidural hemorrhage, subdural hemorrhage, and subarachnoid hemorrhage in both PVP and PKP. As a result, it is necessary to evaluate the patient\' s body before surgery carefully, especially in the case of blood coagulation. This article reports a case of autoimmune disease patient admitted to Peking University People\' s Hospital due to lumbar 4 vertebral compression fracture combined with Sjögren\' s syndrome. The patient\' s preoperative examination showed that the activated partial thromboplastin time (APTT) was significantly prolonged. After completing the APTT extended screening experiment and lupus anticoagulant factor testing, the multi-disciplinary team (MDT) of Peking University People\' s Hospital jointly discussed the conclusion that the patient\' s test results were caused by an abnormal self-immunity anti-copulant lupus (LAC). Based on the results of the laboratory examination, the patient was considered to be diagnosed with combined antiphospholipid syndrome (APS). For such patients, compared with the patient\' s tendency to bleed, we should pay more attention to the risk of high blood clotting in the lower limbs of the patient, pulmonary clots and so on. With timely anti-coagulation treatment, the patient safely passed the peripheral period and was successfully discharged from the hospital. Therefore, for patients with autoimmune diseases with prolonged APTT in the perioperative period, doctors need to carefully identify the actual cause and carry out targeted treatment in order to minimize the risk of surgical and perioperative complications and bring satisfactory treatment results to the patients.

OBJECTIVE: Prevention of pre-analytical issues in coagulation testing is of paramount importance for good laboratory performance. In addition to common issues like hemolysed, icteric, or lipemic samples, some specific pre-analytical errors of coagulation testing include clotted specimens, improper blood-to-anticoagulant ratio, contamination with other anticoagulants, etc. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are very commonly affected tests due to pre-analytical variables. The impact these parameters possess on surgical decision-making and various life-saving interventions are substantial therefore we cannot afford laxity and casual mistakes in carrying out these critical investigations at all.
METHODS: In this case series, a total of 4 cases of unexpectedly deranged coagulation profiles have been described which were reported incorrectly due to the overall casual approach towards these critical investigations. We have also mentioned how the treating clinician and lab physician retrospectively accessed relevant information in the nick of time to bring back reassurance.
CONCLUSIONS: Like every other critical investigation, analytical errors can occur in coagulation parameters due to various avoidable pre-analytical variables. The release of spurious results for coagulation parameters sets alarm bells ringing causing much agony to the treating doctor and patient. Only a disciplined and careful approach taken by hospital and lab staff towards each sample regardless of its criticality can negate these stressful errors to a large extent.

BACKGROUND: Coagulation factor V deficiency is rare, and perioperative management of patients with this condition is particularly important, especially during major abdominal surgery. We present a case of a patient with pancreatic duct stones combined with coagulation factor V deficiency. We share our perioperative management experience.
METHODS: A 31-year-old man presented with recurrent upper abdominal pain for 2 years.
METHODS: The diagnosis of pancreatic duct stones in the patient has been established through abdominal computed tomography and magnetic resonance imaging examinations. The diagnosis of factor V deficiency was initially identified through coagulation function tests, revealing significant prolongation of both aPTT and PT. Subsequent testing of coagulation factors and inhibitors demonstrated that the patient has a deficiency in coagulation factor V. Finally, genetic testing revealed that the factor V deficiency in this case is hereditary.
METHODS: The patient underwent a partial resection of the pancreatic head, and FFP was infused 1 hour before surgery. 600 mL of FFP was instilled 1 hour before the start of surgery along with 10 U of cryoprecipitate. and 600 ml of FFP were added during surgery. Postoperative treatment included intermittent FFP supplemental infusion in the first 5 days after surgery while monitoring the coagulation function.
RESULTS: The patient underwent a successful surgery without any abnormal bleeding or oozing during the procedure. The postoperative recovery was smooth, with no abnormal bleeding.
CONCLUSIONS: Patients with a deficiency of coagulation factor V are not contraindicated for surgery. Appropriate Fresh Frozen Plasma (FFP) replacement therapy can ensure the safe conduct of the surgical procedure. For patients with abnormal blood coagulation function, we recommend testing for coagulation factors and inhibitors, as well as performing genetic testing for abnormal coagulation factors, which can provide guidance on marriage and childbirth.

BACKGROUND: Factor XII deficiency can be related to either homozygous or compound heterozygous pathogenic variants in the F12 gene. The disease is commonly known as Hageman trait and is inherited in both autosomal recessive or dominant patterns. Clinically, factor XII deficiency is not associated with bleeding but conversely has been linked to thrombotic events, recurrent pregnancy loss, and hereditary angioedema. Molecular data of F12 deficiency are scarce and have revealed varying results between cases. However, most of the reported variants are missense mutations, gross deletions, or small insertion. Factor XII deficiency has been reported in the Saudi population in several studies, either as isolated case reports or included within the studies of rare bleeding factors deficiency. However, molecular data are lacking as no case report of genetic studies related to factor XII deficiency has been published in our local population, to the best of our knowledge.
METHODS: Herein we describe a homozygous missense variant involving exon 12 within F12 gene (5:176,830,269 G>A; p.Gly506Asp) in a 36-year-old Saudi multiparous female referred from the surgical clinic with significantly high activated partial thromboplastin time during preoperative assessment for sleeve gastrectomy. The patient had no history of bleeding episodes during the previous deliveries nor any tooth extractions. She had single event of spontaneous abortion during the 15th week of gestation without any bleeding complication. There was no history of thrombosis or skin manifestations, and she was not taking any medicines. There was no family history of bleeding or thrombosis. Family history revealed consanguinity as the parents are first-degree cousins. Physical examination was unremarkable. Upon investigation, the prolonged activated partial thromboplastin time was fully corrected by a 1:1 mixing study with normal pool plasma while lupus anticoagulant tests were negative. Factor assays and von Willebrand factor tests are all within normal ranges except for factor XII, which was severely deficient. A homozygous missense variant involving exon 12 within F12 gene (5:176,830,269 G>A; p.Gly506Asp) was identified.
CONCLUSIONS: F12 (5:176,830,269 G>A; p.Gly506Asp) variant is likely to be a pathogenic variant among homozygous factor XII-deficient patients. Genetic counseling and management of the patients and families should be based on clinical evaluation.

Whereas lupus anticoagulant (LA) and anti-factor VIII (anti-VIII) antibody are both acquired autoimmune coagulation inhibitors, they exhibit different pathophysiologic mechanisms and opposite clinical manifestations. Distinguishing between these two inhibitors is therefore essential for optimizing appropriate management. Harboring both antibodies, which is a rare condition, is of a challenging and confounding laboratory work-up.
We illustrate a case report of a 39-year-old man admitted for the management of recurrent deep-vein thrombosis. Curiously, the initial physical examination revealed several hematoma and bruises of varying sizes. Biologically, a prolonged activated partial thromboplastin time (APTT) was objectified and was not corrected by the mixing study. The following detection of synchronous LA and anti-VIII was made using specific assays.
Through this case, we illustrate the complexity of diagnosing coexistent LA and FVIII inhibitors. In fact, the biological hallmark of both inhibitors is an isolated prolonged APTT that does not correct by the mixing study. Despite the progress in LA and anti-VIII assays and the ongoing updating of standardized recommendations, the lack of specific tests for LA and the limited availability of VIII quantification tests other than the clot-based assays make it difficult to distinguish adequately between the two inhibitors. Therefore, it is crucial to correlate test results with clinical features and patient evaluation.

The aim of this article is to describe a case in which protamine was used for a low-molecular-weight heparin (LMWH) overdose and present an up-to-date review of the literature on the management of LMWH overdose in adults.
An unintentional administration of enoxaparin 900 mg occurred in a 73-year-old man with coronavirus disease 2019-related pulmonary embolism. Management of the overdose included a protamine bolus followed by an infusion. Anti-factor Xa levels and activated partial thromboplastin time were monitored. Anti-factor Xa levels declined in a linear fashion irrespective of protamine administration. No bleeding or further thrombotic complications occurred in the patient. A review of the literature revealed that the optimal strategy to treat an LMWH overdose is unknown, with treatment of overdoses ranging from clinical observation to aggressive protamine dosing in reported cases. Although protamine effectively neutralizes unfractionated heparin, it is unable to completely reverse LMWH activity and has variable effects on laboratory measures of LMWH anticoagulant activity.
The current case report provides additional data to previous literature suggesting that protamine may have a limited effect in decreasing anti-factor Xa levels in LMWH overdose. Continued reporting on the management of LMWH overdoses is warranted to clarify the optimal treatment strategy.

We report a case of a patient with recurrent hematomas while on anticoagulation for a pulmonary embolism and a prolonged hospital stay due to a delayed diagnosis for acquired hemophilia A. Acquired hemophilia A is a rare autoimmune bleeding disorder with autoantibodies directed against coagulation factor VIII (FVIII), leading to an acquired FVIII deficiency. A prolonged isolated activated partial thromboplastin time (aPTT) in a bleeding patient warrants workup for acquired hemophilia A. This is specifically challenging in patients with thrombosis on anticoagulation and can lead to significant delays in diagnosis and associated morbidities. The case highlights the need for further awareness of this disease, potential laboratory pitfalls when conducting and interpreting coagulation assays, and the management considerations in a patient with a simultaneous thrombotic and hemorrhagic condition.