Normal Coagulation Profile Research Articles

Evans Syndrome: A Case Report

Evans syndrome, a combined clinical condition of autoimmune haemolytic anaemia (AHA) and idiopathic thrombocytopaenic purpura (ITP) and has non-specific pathogenesis. The clinical cases are extremely rare, since only 4% of AHA or ITP are incorporated with Evans. It is distinguished from differentials, such as lupus, IgA deficiency, and acquired immunodeficiency, by peripheral blood film, bone marrow, Coombs test, and coagulation profile. A case of adult female from Pabna, Bangladesh is documented in this report. She complained of high grade intermittent fever, exertional dyspnea, icteric skin and sclera. Other features included mild splenomegaly, dark urine, and profuse sweating after fever. Investigation reports were consistent with AHA and ITP, with normal coagulation and viral profile. However, the patient was treated with corticosteroids, platelet and blood transfusion. And in follow-up visits, there was a pattern of gradual decline in erythrocyte sedimentation rate (ESR) and reticulocyte count, with normalization of haemoglobin, red cell, and white cell count. No association with other diseases was found in this case.
 Bangladesh Med J. 2018 Jan; 47 (3): 37-40

2306 Hydroxychloroquine-Induced Acute Liver Injury

INTRODUCTION: Hydroxychloroquine is a commonly prescribed medication with antimalarial and anti-inflammatory properties. A very rarely reported side effect of this medication is drug induced acute liver injury. CASE DESCRIPTION/METHODS: A 62-year old female with a history of rheumatoid arthritis, on long term prednisone, presented to the emergency department with two day history of arthralgias, generalized weakness, and fever of 104 F. She had no history of alcohol use or any risk factors for viral hepatitis. Clinical exam was unremarkable. Laboratory data showed Aspartate aminotransferase (AST) or 798 IU/L and Alanine aminotransferase (ALT) of 1254 IU/L, with normal serum bilirubin, alkaline phosphatase and coagulation profile. Serologic tests for viral etiology including Hepatitis A, Hepatitis B, Hepatitis C, Cytomegalovirus, Epstein-Barr virus, and Human immunodeficiency virus were non-reactive. Anti-nuclear antibody, smooth muscle antibody, and anti-double-stranded DNA antibody were unremarkable. Her urine and blood cultures showed no growth. Abdominal ultrasound showed an echogenic liver consistent with hepatic steatosis and no evidence of biliary obstruction. Chest X-ray was normal. Upon review of her medications, patient had started hydroxychloroquine two weeks prior to admission. The medication was discontinued upon admission, after which she continued to improve. At follow up ten days later, she remained asymptomatic and her liver function tests continued to improve with AST of 46 and ALT of 161. DISCUSSION: Acute transaminitis due to hydroxychloroquine is rare. Only four reported cases have been noted per literature review. Mechanism of injury to hepatic cells is unknown however the drug is metabolized in the liver and may alter the metabolism of other drugs. Porphyria cutanea tarda is a disease that may be treated with low doses of hydroxychloroquine. It is known that higher doses of hydroxychloroquine usually greater than 100 mg twice a week can trigger acute liver injury in patients with history of Porphyria cutana tarda. These patients present with sudden onset of fever and marked serum enzyme elevations with increased excretion of porphyrins and photosensitivity. The presented patient in the case report did not have underlying Porphyria cutanea tarda.

2393 A Unique Case of Liver Disease in Pregnancy

INTRODUCTION: Pregnancy-related liver disease is seen in up to 3% of all pregnancies. Pregnancy-related etiologies include hyperemesis gravidarum, pre-eclampsia, HELLP, intrahepatic cholestasis of pregnancy, and acute fatty liver of pregnancy (AFLP). Given the significant morbidity and mortality associated with these conditions, there is a need for early recognition. Here we present a unique case of pregnancy-related liver disease in an asymptomatic patient. Despite a thorough evaluation for liver and non-liver related causes, her lack of symptomatology and associated laboratory findings made establishing a definitive diagnosis difficult. CASE DESCRIPTION/METHODS: 30 year-old woman G1P0 at 29 weeks gestation with dichorionic triamniotic triplets presented with generalized weakness. Her past medical and surgical histories were otherwise non-contributory and her only medication included prenatal vitamins. The physical exam was unremarkable except for a gravid uterus. Throughout her hospital course, she remained normotensive. Admission labs were significant for an abnormal liver profile: AST 200 U/L, ALT 349 U/L, ALP 121 U/L, and total bilirubin 0.5 mg/dL, compared to a previous normal baseline. Complete blood count and renal function were normal. Abdominal ultrasound (US) showed increased liver echogenicity consistent with fatty liver disease. Additional work-up revealed a normal coagulation profile, fibrinogen, lactate dehydrogenase, and haptoglobin. Urinalysis was negative for proteinuria. Serologies for viral and autoimmune hepatitis were negative. Total bile acids were mildly elevated at 9.3 umol/L (normal < 6.8umol/L) and 24-hour urinary copper was normal. Though she remained asymptomatic, liver enzymes continued to uptrend. On day 16 she underwent urgent C-section due to rising liver enzymes and evidence of fetal distress. Liver enzymes continued to rise until POD1 before rapidly declining. DISCUSSION: This was a unique case of pregnancy-related liver disease of unknown etiology, but most consistent with an early manifestation of AFLP. We suspected AFLP based on the steatosis noted on US, however, since we could not check her children for LCHAD deficiency a definitive diagnosis could not be made. Surveillance US showing resolution of steatosis would have helped confirm the diagnosis however the patient was lost to follow up. This was an interesting presentation of AFLP as most cases are discovered in women presenting with acute liver failure; this case was unique in that it was discovered unexpectedly.

REFRACTORY HEMORRHAGIC SHOCK SECONDARY TO ACQUIRED HEMOPHILIA A

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Hemorrhagic shock is a potentially lethal condition encountered in the intensive care unit. Recognition of the bleeding source and coagulopathic comorbidities is imperative. Acquired factor VIII inhibitor is a rare but devastating cause of hemorrhagic shock. CASE PRESENTATION: An elderly woman who recently sustained a humeral fracture complicated by pain and excessive Ibuprofen use was admitted with hematemesis. She had a bleeding gastric ulcer which was endoscopically treated without complication. She required 6 units of blood and was discharged home. A week later, she was re-admitted with a syncopal episode. Her hemoglobin was 6.1 g/dL. Computed tomography (CT) showed retroperitoneal (RP) bleeding. She was transferred to our tertiary hospital and was found to be in shock. Blood work revealed prolonged activated prothrombin time and normal prothrombin time. She had not received heparin products in over 3 weeks. Mixing studies did not correct the defect, suggesting the presence of an inhibitor. Testing of factor VIII showed reduced activity at 8%. A Bethesda assay confirmed very high titers of factor VIII inhibitor (1:64). She was started on massive transfusion protocol and Factor VIII Inhibitor Bypassing Activity (FEIBA) infusion. Patient had 2 cardiac arrests followed by return of spontaneous circulation (ROSC). Repeat CT angiography showed enlarging RP hematoma. Interventional radiology angio-embolized multiple arteries with endovascular coils; however, a clear bleeding source could not be identified. The patient had two more cardiac arrests and progressed to multi-organ system failure. After a family meeting, she was transitioned to comfort care and passed away. DISCUSSION: Factor VIII inhibitors are the most common acquired inhibitors of coagulation. Acquired hemophilia A is a rare condition with poorly understood etiology often associated with pregnancy, rheumatologic diseases, malignancies or drug reactions. Our patient had a normal coagulation profile prior to her gastrointestinal bleed requiring transfusion of blood products. While rare, there have been reports of developing an acquired inhibitor of coagulation after administration of blood products or derivatives. Even with aggressive treatment regimens, mortality remains high, especially with elevated inhibitor titers. CONCLUSIONS: Acquired factor inhibitor is a rare but devastating cause of hemorrhagic shock. Providers should test for an acquired inhibitor of coagulation in patients with spontaneous bleeding in the absence of known trauma or coagulopathy. Despite high mortality rates, early diagnosis with prompt initiation of factor directed therapy is essential. Reference #1: Kruse-Jarres R, Kempton CL, Baudo F, et al. Acquired hemophilia A: Updated review of evidence and treatment guidance. Am J Hematol. 2017;92:695–705. https://doi.org/10.1002/ajh.24777 Reference #2: Kessler, C. M. and Knöbl, P. (2015), Acquired haemophilia: an overview for clinical practice. Eur J Haematol, 95: 36-44. https://doi.org/10.1111/ejh.12689 Reference #3: Kajitani, M. , Ozdemir, A. , Aguinaga, M. , Jazieh, A. , Flick, J. T. and Antakli, T. (2000), Severe Hemorrhagic Complication Due to Acquired Factor V Inhibitor After Single Exposure to Bovine Thrombin Product. Journal of Cardiac Surgery, 15: 378-382. https://doi.org/10.1111/j.1540-8191.2000.tb01296.x DISCLOSURES: No relevant relationships by Salim Daouk, source=Web Response No relevant relationships by Amanda Moyer, source=Web Response No relevant relationships by Ibrahim Raphael, source=Web Response

Acetic acid versus radiofrequency ablation for the treatment of hepatocellular carcinoma: A randomized controlled trial

PurposeThe purpose of this prospective study was to compare the efficacy of percutaneous acetic acid (PAAI) to that of radiofrequency ablation (RFA) in the treatment of small (≤5cm) hepatocellular carcinoma (HCC) using a randomized trial. Material and methodsConsecutive patients with small HCC underwent clinical, biochemical, and imaging evaluation. Those fulfilling the inclusion criteria (Child's A/B cirrhosis, less than 5 HCC nodules, HCC nodules≤5cm diameter, no extrahepatic disease, patent portal vein, normal coagulation profile with informed consent) were randomly assigned to receive RFA or PAAI. Tumor response and survival rate were estimated. Non-inferiority margin of 10% difference was taken for effectivity of PAAI compared to RFA. ResultsOf the 86 patients screened, 55 patients with 67 HCC nodules were included. There were 40 men and 15 women with a mean age of 54.3±10.5 (SD) years (range: 28–71years). Of these, 26 patients had PAAI and 29 had RFA. The clinical, demographic and imaging profiles of the two groups were similar. Complete response was non-inferior to RFA [PAAI 75% and RFA 83.3%, difference 8.3% CI (−12.5% to 29.2%)]. Lower limit of this 95% CI (−12.5%) was lower than the 10% non-inferiority margin difference (8.3%). Survival rates were similar at 12months (PAAI, 81.6% vs. RFA, 71.9%; P=0.68) and at 30months (PAAI, 54.4% vs. RFA, 52%; P=0.50). ConclusionPAAI and RFA have similar efficacy in treating small HCC. PAAI could thus be a cost-effective alternative in situations where RFA is either unavailable or unaffordable.

Effect of 50 mg/kg intravenous tranexamic acid on coagulation assessed by rotational thromboelastometry (ROTEM) in healthy Beagle dogs.

In people, the antifibrinolytic drug tranexamic acid reduces bleeding and the need for blood products with both normal and exaggerated fibrinolysis without increasing the number of thromboembolic events. In dogs, in addition to prevention and treatment of bleeding, higher doses of tranexamic acid can be used to induce vomiting. The objective of this study was to evaluate the effect of a high dose of tranexamic acid on the coagulation of healthy Beagle dogs. A prospective trial was conducted in eight healthy Beagles receiving tranexamic acid for a concurrent trial evaluating different antiemetics. Rotational thromboelastometry (ROTEM) analysis (EXTEM, APTEM, FIBTEM, INTEM) was performed before and 30 minutes after intravenous administration of 50 mg/kg tranexamic acid. ROTEM parameters before and after tranexamic acid administration and between EXTEM and APTEM were compared with Wilcoxon matched-pairs signed rank test and data is presented as median (range). After tranexamic acid administration, FIBTEM clotting time became significantly shorter (p=0.03) from 37 s (28-124 s) to 33 s (27-40 s) and INTEM clot formation time significantly decreased (p=0.02) from 82 s (47-132s) to 60 s (43-107 s). After tranexamic acid APTEM MCF was significantly weaker (p=0.01) with 45 mm (30-63 mm) than EXTEM MCF with 55 mm (43-69 mm) and than APTEM MCF before tranexamic acid with 55 mm (43-69 mm) (p=0.02). All other analysed parameters including maximum lysis did not change after administration of tranexamic acid. The administration of 50 mg/kg intravenous tranexamic acid resulted in small changes in ROTEM profiles without inducing a hypercoagulable clot. In conclusion, tranexamic acid can safely be administered to healthy dogs with normal coagulation profiles. As an additional finding, APTEM parameters measured in the current study do not support the use of this test in dogs.

Cytomegalovirus induced refractory TTP in an immunocompetent individual: a case report

BackgroundThrombotic thrombocytopenic purpura (TTP) is a rare, potentially fatal disease with multisystem involvement. Cytomegalovirus (CMV) infection as a cause of refractory TTP, has been reported only in immunocompromised individuals. We report a case of CMV-induced refractory TTP in an immunocompetent individual.Case presentationA 35-year-old, previously healthy Sri Lankan man, presented with fever for 3 days with gum bleeding and progressive drowsiness. His Glasgow coma scale score was 10/15. He did not have papilloedema or neck stiffness. Laboratory evaluation showed a severe thrombocytopenia with microangiopathic haemolytic anaemia. There was marginal renal impairment and normal coagulation profile. Non-contrast CT scan of brain was normal. A diagnosis of thrombotic thrombocytopenic purpura was made. Despite daily plasma exchanges and high-dose steroids, he failed to achieve the expected therapeutic response, thus demonstrating refractory TTP. On exploring for possible causes of refractoriness to treatment, a clinically significant PCR titre of CMV was detected. Treatment of CMV infection lead to complete recovery of TTP. His disease course was further complicated with spontaneous spinal haemorrhage leading to neurological sequelae.Discussion and conclusionsThis is the first report of CMV induced refractory TTP in an immunocompetent adult. It is also the first report of clinically significant spontaneous spinal haematoma in TTP. These two rare occurrences should be considered when patients with refractory TTP do not improve as expected.

Single Ventricle Physiology Patients and Coagulation Abnormalities: Is There a Relationship With Hemodynamic Data and Postoperative Course? A Pilot Study.

This study evaluates coagulation profiles of single ventricle (SV) patients in relationship to liver function, hemodynamic variables and outcome. Twenty-six children with SV anatomy were included. Advanced coagulation profiles, invasive preoperative hemodynamic parameters and clinical course were retrospectively analyzed. Median (interquartile range) age and weight at the time of blood sampling was 25.5 (31) months and 10.5 (6.9) kg. Sixteen patients (16/26; 62%) showed decreased antithrombin and/or protein C (PC) and/or free protein S (PS) function and/or free PS antigen. Two patients showed abnormal activated PC resistance ratio due to heterozygous factor V Leiden mutation and 1 heterozygous prothrombin G20210A mutation. Group comparison (abnormal coagulation profile [group 1; n = 16] versus normal coagulation profile [group 2; n = 10]) showed longer postoperative hospitalization time (p = .04), longer postoperative catecholamine support (p = .01), a higher incidence of thromboembolic events (p = .04), and chylothoraxes (p = .007) in group 1. In 5 (31%) of 16 group 1 patients, thromboembolic complications occurred: cerebral stroke (n = 1), intestinal ischemia (n = 2), thrombus formation in inferior caval vein (n = 1), and pulmonary vein (n = 1). Abnormalities in coagulation parameters are common in SV patients. Coagulation abnormalities constitute a preoperative risk factor and affect postoperative course.

Vitamin K antagonists and emergencies.

The recent emergence of 'non-VKA' oral anticoagulants may have led to some forgetting that vitamin K antagonists (VKA) are by far the most widely prescribed oral anticoagulants worldwide. Consequently, we decided to summarize the information available on them. This paper presents the problems facing emergency physicians confronted with patients on VKAs in 10 points, from pharmacological data to emergency management. Vitamin K antagonists remain preferable in many situations including in the elderly, in patients with extreme body weights, severe chronic kidney or liver disease or valvular heart disease, and in patients taking VKAs with well-controlled international normalized ratios (INRs). Given the way VKAs work, a stable anticoagulant state can only be achieved at the earliest 5 days after starting therapy. The induction phase of VKA treatment is associated with the highest risk of bleeding; validated algorithms based on INR values have to be followed. VKA asymptomatic overdoses and 'non-severe' hemorrhage are managed by omitting a dose or stopping treatment plus administering vitamin K depending on the INR. Major bleeding is managed using a VKA reversal strategy. A prothrombin complex concentrate infusion plus vitamin K is preferred to rapidly achieve an INR of up to 1.5 and maintain a normal coagulation profile. The INR must be measured 30 min after the infusion. Before an invasive procedure, if an INR of less than 1.5 (<1.3 in neurosurgery) is required, it can be achieved by combining prothrombin complex concentrate and vitamin K. A well-codified strategy is essential for managing patients requiring emergency invasive procedures or presenting bleeding complications.

Clarithromycin-Induced Acute Liver Failure (ALF)

Clarithromycin is a macrolide antibiotic widely used to treat respiratory, skin, and soft tissue infections. Although elevated liver enzymes and cholestatic hepatitis have been infrequently reported, comprehensive literature review reveals only 6 cases of clarithromycin-induced ALF (fig 2). 60-year-old male with history of hypertension and hypothyroidism presented to the hospital with acute asthma exacerbation secondary to respiratory tract infection. Complete blood picture, and liver and kidney function tests were within normal limits. Clarithromycin, prednisone and albuterol inhaler were prescribed, and he was discharged. 10 days later, he represented and physical examination revealed stable vital data but soft, diffusely tender abdomen with hypoactive bowel sounds and no peritoneal signs. Laboratory analysis revealed WBC=12.2bil/L, hemoglobin(hb)=14.5 g/dL and platelets=129bil/L, lipase=33 U/L, lactic acid=0.6 mmol/L, ammonia=22 mcmol/L and normal coagulation profile. Figure 1 highlights the trend of liver function tests (LFTs) during hospitalization. CT of the abdomen with contrast, abdominal ultrasound with doppler and echocardiography were all normal. Viral hepatitis panel (anti-HAV, anti-HBs, anti-HBc, HBs antigen, anti-HCV, HCV-RNA, & anti-HEV), autoimmune hepatitis panel (ANA, AMA, smooth muscle antibody, liver-kidney microsomal antibody, and total immunoglobulin) and atypical viruses (HIV, CMV, and HSV) were insignificant. On third day, he developed altered mental status; Hb dropped to 5.5 g/dL, platelets dropped to 35 bil/L and LFTs worsened. Liver biopsy was canceled due to hemodynamic instability and coagulopathy. Massive transfusion was initiated, but despite aggressive resuscitation, the patient had cardiac arrest and expired. On autopsy, histopathologic analysis of the liver revealed diffuse hepatocellular necrosis with occasional sparing of periportal hepatocytes (fig 3) consistent with the prior reported cases and the pattern of idiosyncratic drug induced liver injury (DILI). There was no evident lobular or portal inflammation, fibrosis, viral cytopathic effect, thromboemboli, or malignancy.2304_A Figure 1. Trend of liver function testsProminent eosinophils in the portal tract or lobules can suggest a drug-induced hypersensitivity reaction but are rarely seen in cases of idiosyncratic drug reactions. There are no defined pathognomonic histopathologic findings of DILI and a high index of clinical suspicion in combination with histopathologic findings are needed for the diagnosis.2304_B Figure 2. Reported cases of acute liver failure from Clarithromycin2304_C Figure 3. A: Low power photomicrograph of H&E section of liver showing geographic areas of necrosis and marked sinusoidal congestion. B: High power photomicrograph of H&E stain of liver showing a central vein (*) with adjacent marked sinusoidal congestion and extensive hepatocyte necrosis.

Acute Esophageal Necrosis Following Kidney Transplantation

Acute esophageal necrosis (Black esophagus) is a rare complication typically seen as a circumferential black appearing esophagus in the less vascularized distal region. Etiologies include hypoperfusion, infectious etiologies (e.g. CMV, Candida albicans), DKA, and toxic ingestion. Two cases have been previously reported in kidney transplant recipients involving intra-operative cardiac arrest with associated hypotension, and primary CMV infection, respectively. Our patient developed acute esophageal necrosis without an episode of hypotension, or infectious etiology. A 48 year-old Asian man with end-stage renal disease due to IgA nephropathy received a deceased donor kidney transplant. Both donor and recipient had positive cytomegalovirus (CMV) IgG antibodies prior to transplant. The patient did not experience intraoperative hypotension. He received standard induction and maintenance immunotherapy including tacrolimus target trough levels between 8 and 10 ng/ml. Post-operatively, the patient developed hiccups, postprandial chest and epigastric pain, dysphagia, and odynophagia. He was afebrile, normotensive, and had no fever or evidence of gastrointestinal bleeding. Labs revealed a stable normocytic normochromic anemia with hemoglobin of 9.8g/dL without evidence of leukocytosis, thrombocytopenia and a normal coagulation profile. At symptom onset, tacrolimus level was slightly elevated at 11.1 ng/ml, and his serum creatinine peaked at 15.4. Hemodialysis was started without symptomatic improvement. On POD 4, patient underwent esophagogastroduodenoscopy (EGD) that demonstrated evidence of diffuse blackdiscoloration, ulceration and erythema in the distal esophagus. Biopsies were consistent with necrosis and showed no evidence of CMV infection. Conservative management including NPO, TPN, and PPI for one week led to marked improvement in symptoms and EGD two weeks later revealed adequate reepithelization and no visualization of necrotic tissue (Figure 1D-F). Despite the absence of frank hypotension, infections or DKA, acute esophageal necrosis may occur in the setting of normal blood pressure and major surgery. It is difficult to determine, but tacrolimus with vasoconstrictive properties could have resulted in distal esophageal hypoperfusion and subsequent necrosis. The current case raises clinician awareness in considering the possibility of esophageal necrosis post-transplant in the setting of dysphagia, odynophagia, and elevated tacrolimus levels.1827 Figure 1. A) Normal-appearing upper esophagus on initial EGD. B) Middle esophageal tissue discoloration, erythema and friability with contact bleeding. C) Lower esophageal tissue friability, ulceration and sloughing. D) Normal-appearing upper esophagus on follow-up EGD one week afterwards. E) Normal-appearing middle esophagus. F) Erythema and evidence of re-epithelization in lower third of the esophagus.

A Rare Case of Cyclical Hemothorax: Thoracic Endometriosis Syndrome

Endometriosis is a common condition in which endometrial cells and stroma are deposited in extrauterine sites. Its prevalence has been estimated to be 10% of reproductive age females. It is commonly found in the pelvis; however, it may be found in the abdomen, thorax, brain, or skin. Thoracic involvement is a relatively rare presentation of this common disease. Thoracic endometriosis commonly presents as pneumothorax in 73% of patients. A rarer presentation of thoracic endometriosis is hemothorax (<14%) or hemoptysis (7%). Thoracic endometriosis is an uncommon cause of a pleural effusion. We present a case of 28-year-old African American female with no other medical conditions. She presented to the hospital with worsening right-sided pleuritic chest pain, dyspnea, and menorrhagia. She had been complaining of pleuritic chest pain for 5 years, the onset of which corresponds to the start of her menstrual cycle and is relieved with cessation of menses. Initial laboratory studies revealed a severe microcytic anemia with normal coagulation profile. Chest X-ray showed small right pleural effusion and suspicious for airspace disease. A computed tomography (CT) of chest was ordered for further clarification and identified large right pleural effusion. CT-guided thoracentesis removed 500 ml of serosanguinous fluid consisting of blood elements. There can be multiple sites involved with endometriosis and can present with wide range of symptoms that occur periodically with menses in young woman. The history and pleural fluid findings of this case are suggestive of Thoracic Endometriosis Syndrome. The diagnosis of this is often missed or delayed by clinicians, which can result in recurrent hospitalization and other complications. As internists we should be suspicious of atypical presentations of endometriosis and treat them early before complications develop. This case also highlights the importance of suspecting atypical etiologies for pleural effusion.

Molecular analysis of gene mutations in eight patients with Glanzmann's thrombasthenia

Objective: To analyze the gene sequencing in eight patients with Glanzmann's thromboasthenia(GT), and combined with clinical manifestations and laboratory findings to investigate the molecular mechanism of GT. Methods: Eight patients who were diagnosed as GT based on platelet aggregation test and flow cytometry were enrolled, as well as 4 pedigrees. Next-generation sequencing was used to analyze all the exons and flanking sequences of αⅡ band β3 gene and also platelet-type bleeding disorders related genes. Gene polymorphism was excluded by retrievaling HGMD and PubMed databases and relative literature. Mutations were confirmed by sanger sequencing. Results: All the eight patients had relatively normal platelet counts and coagulation profiles. But their platelet response to ADP was impaired, and their platelet response to ristocetin was relatively normal. Flow cytometry showed that of the 8 patients, platelet surface αⅡb/β3 was lower than 5% of the normal value in 5 cases, and in 2 cases was 5% to 20% of normal value, and in 1 case there was no significant platelet surface αⅡb/β3 reduction compared with normal level. Gene analysis revealed that five mutations in ITGA2B gene were identified, including c. 1750C>T(p.Arg584Ter), c.1882C>T(p.Arg628Ter), c.814G>C(p.Val272Leu), c.2333A>C(p.Gln778Pro), c.432G>A(p.Trp144Ter). Six mutations in ITGB3 gene, including c. 719G>A(p.Arg240Gln), c.2248C>T(p.Arg750Ter), c.1495T>C(p.Cys499Arg), c.1728delC(p.Ser577ProfsTer92), c.877C>T(p.Gln293Ter), c. 1260G>A were identified. In addition, mutations in genes such as RUNX1, HPS4, MYH9, ACTN1, HPS3 and SETBP1 were identified in patients with GT. Conclusions: Rather than homozygous mutations, heterozygous mutations, especially compound heterozygous mutations, are more common in patients with GT. The pathogenesis of GT may relate to gene mutations such as RUNX1 in addition to the ITGA2B gene and the ITGB3 gene.

Misguided by INR in Liver Disease Patients? Implications for Clinicians Including Pain Proceduralists.

THE ROSY PAST The prothrombin time (PT) assay, developed in 1935, was used in the identification of the anticoagulants dicumarol and warfarin. Currently, this assay is most commonly used to measure the therapeutic activity of warfarin. It was well known that PT results experienced a variation among centers using different reagents, making comparisons challenging. Around the same time came the invention of the international sensitivity index (ISI), allowing for calibration of different batches of thromboplastins to an international standard. To address interlaboratory PT variation, the international normalized ratio (INR), defined as the ratio of a patient’s PT to a control sample raised to the power of the ISI value, was invented in the 1980s. The INR became widely accepted after endorsement by the World Health Organization. This endorsement was only for control of oral anticoagulant therapy, as ISI calibration was specifically developed for comparing samples of patients with normal coagulation profiles to those who were anticoagulated with Coumadin (warfarin; Bristol-Myers-Squibb, New York, NY) for at least 6 weeks.1 Historically, plasma transfusions have been recommended for patients whose PT was found to be 1.5× longer than normal. Early thromboplastins in the United States had an ISI >2.0; therefore, a 1.5× increase in PT would equal an INR of 2.25. Currently, many thromboplastin reagents have an ISI close to 1.0 (World Health Organization standard); therefore, the same sample with a PT 1.5× longer than normal will equal an INR of 1.5. In the past, a PT 1.5× longer than normal indicated a moderate to severe factor deficiency (factor levels <30%), whereas today, the same value indicates only a mild factor deficiency (factor levels >40%).2 Figure 1.: The cascade model of fibrin formation. This model divides the coagulation system into separate redundant pathways (extrinsic and intrinsic) either of which can result in generation of FXa. The common pathway results in generation of thrombin and subsequent cleavage of fibrinogen to fibrin. Many of the enzymes and enzymatic complexes require Ca2+ and binding to active membrane surfaces (PL) for full activity. For simplicity, feedback activation of procofactors to cofactors and the many inhibitors of the various enzymes have been omitted. Reprinted with permission from Smith.4 Ca2+ indicates calcium; Fb, fibrin; Fg, fibrinogen; FXa, activated form of factor X; HMWK, high molecular weight kininogen; K, kallikrein; PK, prekallikrein; PL, active membrane surfaces; TF, tissue factor.

Thrombin generation estimates the anticoagulation effect of direct oral anticoagulants with significant interindividual variability observed.

: Direct oral anticoagulants (DOACs) are increasingly being used, primarily due to their drug stability and patient convenience. Although these drugs have been evaluated to be well tolerated in numerous clinical trials, their impact on in-vivo anticoagulation effect, variability and therapeutic drug level remains unknown. Hence, we aim to study the effect and variability of DOACs on thrombin generation via the calibrated automated thrombogram. Anonymized coagulation specimens from outpatients on warfarin were collected. Pooled normal plasma samples were spiked with increasing concentrations of dabigatran, rivaroxaban and apixaban. Similarly, plasma samples with normal coagulation profiles were spiked with two concentrations each of dabigatran, rivaroxaban and apixaban. Thrombin generation via calibrated automated thrombogram was run using the above samples and compared with a dataset of normal controls. Increasing international normalized ratio was associated with a reduction of endogenous thrombin potential (ETP) and thrombin peak and increasing lag time. Factor Xa inhibitors produced a flattened thrombin generation curve with a reduction of thrombin peak and relative preservation of ETP. Direct thrombin inhibitors produced a reduction of both ETP and thrombin peak and increasing lag time. Seventy-one citrated plasma samples (26 dabigatran, 21 rivaroxaban and 24 apixaban) were evaluated. The two concentrations produced a reduction of thrombin generation parameters with significant interindividual variability compared with neat plasma of 35-93, 13-31 and 18-71% and for dabigatran, rivaroxaban and apixaban, respectively. Thrombin generation can measure the anticoagulation effect of commonly used DOACs, with each drug having a unique thrombin generation profile. The variability noted using the same concentration suggests significant interindividual pharmacodynamic differences, which maybe relevant with respect to efficacy as well as bleeding side effects. Further delineation of the modifiers of interindividual differences is required in the in-vivo setting.

Thromboelastometry profile in critically ill patients: A single-center, retrospective, observational study.

BackgroundTransfusion therapy is associated with increased morbidity, mortality and costs. Conventional coagulation tests (CCT) are weak bleeding predictors, poorly reflecting coagulation in vivo. Thromboelastometry (ROTEM) provides early identification of coagulation disorders and can guide transfusion therapy by goals, reducing blood components transfusion.ObjectiveThe aim of this study is to describe coagulation profile of critically ill patients using ROTEM and evaluate the association between CCT and thromboelastometry.MethodsThis is a retrospective, observational study conducted in medical-surgical intensive care unit (ICU). Adult patients (≥18 years) admitted to ICU between November 2012 and December 2014, in whom ROTEM analyses were performed for bleeding management were included in this study. The first ROTEM and CCT after ICU admission were recorded simultaneously. Additionally, we collected data on blood components transfusion and hemostatic agents immediately after laboratory tests results.ResultsThe study included 531 patients. Most ROTEM tests showed normal coagulation profile [INTEM (54.8%), EXTEM (54.1%) and FIBTEM (53.3%)] with divergent results in relation to CCT: low platelet count (51.8% in INTEM and 55.9% in EXTEM); prolonged aPTT (69.9% in INTEM and 63.7% in EXTEM) and higher INR (23.8% in INTEM and 27.4% in EXTEM). However 16,7% of patients with normocoagulability in ROTEM received platelet concentrates and 10% fresh frozen plasma.ConclusionThe predominant ROTEM profile observed in this sample of critically ill patients was normal. In contrast, CCT suggested coagulopathy leading to a possibly unnecessary allogenic blood component transfusion. ROTEM test may avoid inappropriate allogeneic blood products transfusion in these patients.

Dieulafoy’s disease with mediastinal arteriovenous malformation

A 42-year-old, non-smoker man was hospitalised for newly diagnosed acute myeloid leukaemia and had an episode of haemoptysis of 200 mL fresh blood, complicated by transient hypotension. Patient was afebrile...

Thromboelastometry in trauma care: a place in the 2018 Belgian health care system?

ABSTRACTIntroduction Evidence supporting the use of Thromboelastography (TEG®) and rotational thromboelastometric (ROTEM®) in the trauma setting remains limited. We present the results of a practical evaluation of the potential interest of ROTEM® in the diagnosis of acute coagulopathy and the need for emergent blood product transfusion in the general trauma population of a non-trauma Belgian emergency department.Methods Extracting a convenience cohort from the initial prospective TICCS study, we performed a retrospective analysis to test the following hypothesis: ROTEM® might be helpful to discriminate trauma patients with or without acute coagulopathy. Fifty patients were included and ROTEM® results were compared to conventional coagulation tests results, blood transfusion need and outcome.Results With a negative predictive value of 97.6% and a positive predictive value of 42.9%, a strictly normal ROTEM® profile at the time of admission seems to be able to exclude the presence of acute coagulopathy. ROTEM® also seems to be accurate in identifying patients without the need for emergent blood product transfusions.Conclusion In a population of trauma patients of a Belgian general emergency department, a strictly normal coagulation profile evaluated by ROTEM® at hospital entry is associated with a normal coagulation profile evaluated by INR and fibrinogen levels and the absence of any indication of blood product transfusion. ROTEM® may be useful for preselection of trauma patients at risk for coagulopathy within the global trauma population. This, however, would need confirmation in further investigations.Trial registration: clinicaltrials.gov NCT02132208 Registered 6 May 2014.

Antepartum Eclampsia and Partial HELLP Syndrome in a Patient with Bell\'s Palsy

Bell's palsy affects pregnant women three times more often than nonpregnant women, with majority of cases occurring in the third trimester (71%) and early postpartum period (21%). Bell's palsy during pregnancy has been associated with preeclampsia, with 22% of these women developing preeclampsia. A 26-year-old G3P1 L1A1 diagnosed with Bell's palsy 2 weeks earlier, presented at 33-week period of gestation with a chief complaint of progressive bilateral pedal edema for 1 week, blood pressure (BP) - 150/100 mmHg and dipstick urine - 3+. Laboratory screening of HELLP syndrome was normal. Six days later, she had an episode of generalized tonic–clonic convulsion, magnesium sulfate was given, and emergency laboratory investigations revealed partial HELLP syndrome (platelet - 80,000, serum glutamic oxaloacetic transaminase/serum glutamic pyruvic transaminase - 281/222 U/L) with normal coagulation profile. Lower segment caesarean section was performed with delivery of a 2ks neonate with APGAR of 7/10 and 9/10 at 1 and 5 minute respectively. Postoperative day 3, all laboratory reports including magnetic resonance imaging brain were normal. BP was stabilized and she was discharged on the third postnatal day, with some right-sided residual facial weakness. All obstetricians must be aware of association of Bell's palsy with hypertensive disorders of pregnancy and aggressively screen for the same as soon as diagnosed, to prevent complications such as eclampsia and HELLP. Since Bell's palsy is not associated with adverse perinatal outcomes, it should not prompt obstetricians for hastening deliveries prematurely.

Orange Coloured Urine Following a Lower Segment Cesarean Section: A Case Report

Presence of high colored urine is an indicator of a systemic abnormality, most of genitourinary. The other causes could point out to hepatic abnormalities, resulting in a coagulation dysfunction. However, it is uncommon to find a post partum case of high colored urine in the absence of any local or systemic pathology. This study reports a rare case of orange coloured urine in a 25 year old lady on the first day of Lower Segment Cesarean Section. The primi, reported a history of recurrent urinary tract infections and she was diagnosed with Pregnancy Induced Hypertension during her antenatal period. Following admission at 36 weeks, she delivered through LSCS a normal 2.2 kg weighing baby with a good APGAR. On the first post operative day, she reported orange discoloration of her urine. Routine blood investigations revealed normal renal, hepatic and coagulation profiles. A urine analysis and culture revealed presence of urinary infection with Klebsiella pneumonia. On treatment with sensitive antibiotics, the discoloration disappeared and the urine was free of bacteria. The mechanism of high colored urine was proposed to be due to the presence of indirubin, as a result of breakdown of tryptophan by the bacteria in an alkaline environment. This case report elucidates the need for constant vigil for an early diagnosis in order to prevent complications.