Elevated Partial Thromboplastin Time Research Articles

Hemophagocytic Lymphohistiocytosis As an Immune-Related Adverse Events in a Patient with Advanced Lung Adenocarcinoma

I ntroduction: Immune checkpoint inhibitors (ICIs) have been approved as single agents or in combination with cytotoxic chemotherapy for use in the treatment of different tumor types including skin, lung, kidney, endometrium, bladder..., especially in advanced stages. ICIs are usually well tolerated and despite their demonstrated clinical benefit, severe immune-related adverse events (irAEs) can sometimes occur, including colitis, hepatitis, myocarditis, glomerulonephritis, pneumonitis, hypophysitis... Here we are reporting a case of hemophagocytic lymphohistiocytosis (HLH), a rare but potentially life-threatening complication of ICI therapy. Case presentation: We present the case of a 60-year-old female with metastatic adenocarcinoma of left lung who presented to the emergency room with a week history of generalized weakness, worsening dyspnea on exertion and decreased appetite while on maintenance ICI with pembrolizumab for approximately 1 year. On admission vital signs were a blood pressure of 88/70mmhg, pulse rate of 139 beats per minute, respiratory rate of 20 cycles per minute, temperature of 98.3°F and oxygen saturation of 98% on room air. Physical exam was unremarkable. A complete blood count revealed leukopenia of 2.7k/uL, hemoglobin of 11.8 g/dL, and mild thrombocytopenia of 131k/uL. A basic metabolic panel was significant for hyponatremia of 133 mmol/L, blood urea nitrogen of 43mg/dL, and creatinine of 1.71mg/dL. She was started on empiric broad-spectrum antibiotics with IV vancomycin and cefepime due to concern for infection in the setting of recurrent febrile episodes and neutropenia. Worsening pancytopenia prompted further work-up and showed elevated ferritin of 19581, lactate dehydrogenase of 2380, folate > 20, vitamin B 12 of 1645, iron level of 62, elevated total and direct bilirubin of 6.3 and 2.9 mg/dL, haptoglobin < 10 mg/dL, fibrinogen level of 174, C- reactive protein of 73.9. Elevated soluble IL2- receptor elevated at 10336.7, d-dimer > 20, elevated partial thromboplastin time of 51.1, Prothrombin Time of 20.5, INR of 1.7. Peripheral blood smear was unremarkable. Hemophagocytic lymphohistiocytosis was suspected and a bone marrow was performed prior to initiation of intravenous steroids. Bone marrow showed evidence of abundant histiocytes with hemophagocytosis of nucleated cells. She was discharged on an oral steroid taper. She has since been well without evidence of tumor progression off therapy for over 2 years now. Discussion: HLH is a rare but potentially life-threatening complication of ICI therapy that requires prompt recognition and management. Our patient responded well to steroids and did not require cytotoxic chemotherapy with etoposide.

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

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

Barotrauma in a Previously Healthy and Young COVID-19 Patient: an Autopsy Case Report

Abstract Introduction/Objective Since the emergence of a novel SARS-CoV-2 virus caused coronavirus disease 2019 (COVID-19), a great number of autopsy studies have been published. However, histopathologic studies focused on pulmonary barotrauma are very rare. Here we report an autopsy confined to the lungs on a young COVID-19 patient. Methods/Case Report The patient was a 37-year-old male, non-smoker, with no significant past medical history, and a body mass index of 24.1, who presented with shortness of breath and cough. A computerized tomography (CT) showed features of atypical pneumonia. The main abnormal laboratory data included elevated partial thromboplastin time, fibrinogen, and D-Dimer. The patient had been on mechanical ventilation for 35 days, and was complicated by recurrent pneumothoraces, hypotension, and worsening hypoxia. An autopsy limited to the lungs was performed after the patient expired. Grossly, the lungs showed increased weight, adhesions on visceral pleural surface, patchy consolidation and dilated subpleural cysts. Histological examination revealed cystically dilated/remodeled airspaces with extensive coagulative necrosis, focal alveolar hemorrhage and edema, focal confluent fibrosis, and subpleural blebs. Fresh fibrinous thrombi were seen in small- and medium-sized vessels. Viral cytopathic changes or significant inflammation were not observed. The findings in the lungs were consistent with barotrauma in COVID-19. Results (if a Case Study enter NA) NA. Conclusion This case demonstrates various histopathologic changes of the lungs in a previously healthy and young COVID-19 patient with prolonged hospital course of mechanical ventilation. The features of diffuse alveolar damage with inflammation usually seen in the early stage of barotrauma are not identified. Our findings in the lungs may represent the histopathologic characteristics of the later stage of barotrauma in COVID-19.

A Nonimmune Hydrops Case.

A Nonimmune Hydrops Case.

Laboratory markers and risk of secondary hemorrhagic complications after anticoagulation due to venous thromboembolism in the early postoperative phase after neurosurgical procedures

Deep venous thromboses (DVT) and venous thromboembolisms (VTE) are serious complications after neurosurgical procedures. Hemorrhagic complications of thera-peutic anticoagulation on the other hand are also highly dreaded due to the high risk of permanent neurological deficit. Clear guidelines concerning dosage and duration of anticoagulation still do not exist for neurosurgical practice. Over a 10-year episode, patients with postoperative DVT or VTE were retrospectively identified and demographic risk factors as well as routine laboratory coagulation parameters were assessed. The goal was to determine patients at risk for a severe course of thrombosis and complications due to anticoagulation. In total, 173 patients with DVT or VTE were identified. Clinical effect of thrombosis was severe in 32.4% and fatal in 5.8% of all patients. Spinal surgery was associated with a higher risk of major or fatal outcome of thrombosis as compared to cranial procedures (fatal: 12.1 vs. 4.3%, p = 0.035). Elevated partial thromboplastin time, low platelet levels and low quick on diagnosis of thrombosis were associated with a fatal clinical course (p = 0.02, 0.04 and 0.02 respectively). Severe hemorrhagic complications on the other hand occurred in 6.6%, 0.6% were fatal. D-dimer did not predict the course of DVT/VTE but higher levels of D-dimer on day 3 after diagnosis of DVT/VTE were associated with a higher risk of severe bleeding complications (cutoff 4.95 µg/mL). Partial thromboplastin time after initiation of anticoagulation was not associated with hemorrhagic complications and might thus be not helpful to determine the risk of bleeding complications during the early postoperative phase. D-dimer might be of additional use to detect early bleeding complications.

P.157 Frame-based stereotactic brain biopsy: A retrospective review of diagnostic yield and complications at a Canadian Center

Background: Historically, frame-based stereotactic brain biopsy (SBB) has played an important role in the diagnosis of intracranial lesions. We performed a single centre analysis of the outcomes and efficacy of SBB at the London Health Sciences Centre (LHSC). Methods: We performed a retrospective chart review of frame-based SBB from 2006 to 2017 at the LHSC. Intra-operative and final pathology reports were analyzed for biopsy diagnosis and the diagnosis was compared with pre-operative neuroimaging reports for correlation. SBB-associated morbidity and mortality were investigated using chart review and post-operative neuroimaging. Results: 173 consecutive patients were identified. The overall morbidity rate was 8.7% (15 cases) and mortality rate was 0.6% (1 case). Final biopsy diagnostic accuracy was 96%, intra-operative diagnostic accuracy was 94% and pre-operative imaging diagnostic accuracy was 65%. Elevated partial thromboplastin time and the presence of hemorrhage on post-operative CT were associated with neurological morbidity and mortality. The need to obtain three or greater samples the time of biopsy was associated with non-diagnostic biopsy. Conclusions: At the LHSC, SBB is a relatively safe and effective surgical procedure with high diagnostic yield and relatively low risk of complications. Intra-operative pathology has a high efficacy in determining diagnosis when compared to final pathology.

Detecting coagulopathy in pediatric patients with post-tonsillectomy hemorrhage

IntroductionPost-tonsillectomy hemorrhage (PTH) is a serious complication after a tonsillectomy. Utility of lab work at presentation for PTH was low. This study aims to determine the frequency and type of labs drawn at emergency department (ED) presentation and assess the incidence of uncovering a previously unidentified coagulopathy. MethodsA retrospective chart review was performed on pediatric patients who were seen in the ED after tonsillectomy at a tertiary care children's hospital from 2017 to 2019. Exclusion criteria were the following: no tonsillar bleed, history of known coagulopathy, treated by outside provider, ≥18 years old. Lab work included complete blood count (CBC), prothrombin time (PT), partial thromboplastin time (PTT), and von Willebrand factor (VWF). Results364/723 (50.3%) patients met inclusion criteria. 179/364 (49.2%) patients were male and 309/364 (84.9%) patients were Caucasian. Average age at surgery was 8.12 years (SD = 4.0) and average post-operative day at presentation was 6 days (SD = 2.1). Operative control of bleed was performed in 68/364 (18.7%) patients. 334/364 (91.8%) patients had labs drawn in the ED. 64/334 (19.1%) patients were anemic (hemoglobin (Hgb) < 11), 46/334 (13.8%) patients had thrombocytosis (platelets>450,000), 10/334 (3.0%) had elevated PTT and 8/334 (2.4%) had elevated PT. Hematology was consulted in 14/364 (3.8%) patients of whom 6/14 were diagnosed with von Willebrand disease and 1/14 with factor VII deficiency. Aminocaproic acid was used in 8/364 (2.2%) patients due to elevated PTT in 3/8 and multiple episodes of bleeding in 5/8.3/364 (0.8%) patients needed a blood transfusion. No difference was found in incidence of abnormal lab work in patients who did and did not need operative control of bleed (p = .125). Of the 334 patients who had ED labs drawn, 7 (2.1%) had an uncovered coagulopathy. ConclusionUncovering incidental coagulopathies is rare in patients who present with PTH. Though anemia was the most common abnormality noted, only a small percentage required transfusion, with all having abnormal vital signs. Thrombocytosis was the next common abnormality, and this can be seen in an inflammatory state. Developing algorithms is necessary to better guide appropriate lab work in patients who present with PTH and to provide optimal value of care to patients.

Characterization of organ dysfunction and mortality in pediatric patients with trauma with acute traumatic coagulopathy

BackgroundTraumatic injuries are a leading cause of mortality and morbidity in pediatric patients and abnormalities in hemostasis play an important role in these poor outcomes. One such abnormality, acute traumatic...

The Yield and Safety of Skin Biopsies in Acute Myeloid Leukemia Patients during Intensive Chemotherapy Treatment

Introduction: Skin eruptions in acute myeloid leukemia (AML) patients are not uncommon. Skin biopsy is a minimal invasive procedure, yet potential complications, such as infection and bleeding, might be expected in these patients due to immunosuppression and thrombocytopenia. Data are scarce regarding the prevalence, etiology and characteristics of skin eruptions among AML patients during intensive therapies. Even less is known regarding the safety and diagnostic yield of skin biopsies in this setting. We sought to evaluate the diagnostic yield and safety of skin biopsies obtained from adult AML patients during hospitalization for intensive chemotherapy. Methods: This is a single-center retrospective cohort study of adult AML patients who underwent skin biopsies for histopathology and tissue culture during induction and consolidation treatment for AML at our hemato-oncology unit between 1.1.2007-1.9.2018. Data collection included demographic details, AML characteristics, chemotherapy regimens, clinical description of rush and associated symptoms (mainly fever, pruritus) and laboratory tests. We recorded whether biopsy results had an impact on patients' care. This study was approved by the Institutional Review Board. Results: 37 skin biopsies from AML patients were identified in our cohort during the study period. Patient demographics and rash characteristics are presented in Table 1. 22% of the skin biopsies were performed at AML presentation prior to chemotherapy, and the remainder after chemotherapy commencement, i.e. after starting either induction or post-induction (consolidation or salvage) treatment (70% and 8%, respectively). Most skin eruptions were grade 1 (53%) or 2 (26%) in severity. Only 21% were grade 3 and 4 rashes. The most common body parts involved were the limbs (51%) and trunk (33%). At the time of skin biopsy 43% of patients had associated fever and 11% had bacteremia. Most patients (62%) had grade 4 neutropenia and 38% and 19% of patients had grade 3 and 4 thrombocytopenia, respectively. Elevated prothrombin time was evident in 66% of patients, whereas 5.5% of patients had an elevated partial thromboplastin time at the time of biopsy. Rash etiology according to skin biopsies histopathological findings consistent with drug eruptions (24.3%), infections (11%), leukemia cutis (16.2%), Sweet syndrome (5.5%) or a reactive process (8%). 35% of biopsies results were inconclusive. In 16 cases (43%) tissue cultures were performed and of those, 4 cultures were positive. However, only in 1 patient the positive culture result has led to a change of antimicrobial coverage. A proactive approach following biopsy results was conducted in 2 additional patients, when a suspected drug leading to the eruption was discontinued (n=1), and systemic steroids were prescribed instead of acyclovir (n=1). Hence, skin biopsy results changed patients' management only in 8% of cases (n=3). Skin biopsies were generally safe and only 1 patient suffered from a complication directly attributed to the biopsy - i.e. she became febrile and suffered from a local hemorrhagic bulla formation, necessitating administration of vancomycin. Conclusions: We suggest that skin biopsies from AML patients hospitalized for intensive chemotherapy treatment are relatively safe. Nevertheless, their diagnostic yield is limited and does not alter the management of most patients. Increased physician discretion should be exercised prior to performing a skin biopsy in this patient population, to avoid unnecessary usage of medical resources and invasive procedures. Further studies are needed to establish the role of skin biopsies in these patients. Disclosures Wolach: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaker; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaker.

Partial Thromboplastin Time: Accurate Measurement Through Evidence-Based Practice.

At the University of Pittsburgh Medical Center's Hillman Cancer Center, multiple occurrences of critically elevated partial thromboplastin time (PTT) levels drawn by central venous access devices (implantable ports) were determined to be inaccurate. Root cause analysis revealed the institutional policy and staff education for collection did not support peripheral venipuncture for coagulation panels. Peer-reviewed literature and case studies were evaluated by the evidence-based practice council, and the data revealed that PTT levels yielded incorrect results when drawn through an implantable port. This suggested that peripheral venipuncture might be preferable.

Relationship between mean platelet volume, low-grade systemic coagulation and vitamin D deficiency in canine visceral leishmaniasis

Canine visceral leishmaniasis is associated with cardiac changes. This study was designed to test the hypothesis that vitamin D and coagulation parameters, such as D-dimer, activated partial thromboplastin time (APTT), partial thromboplastin time (PT), mean platelet volume (MPV), and white blood cell (WBC) levels, change in different stages of canine visceral leishmaniasis (CVL). Thirty-two dogs diagnosed with CVL were classified into four different groups: stage I (mild disease), stage II (moderate disease), stage III (severe disease), stage IV (very severe disease), and healthy controls. The groups were based on clinical signs, rapid ELISA/IFAT, hematological and serum biochemical tests, and urinary protein/creatinine ratios. Serum vitamin D levels were positively correlated with MPV (r = 0.503), but negatively correlated with D-dimer (r =-0.326), APTT (r =-0.361), PT (r =-0.289), and WBC (r = -0.384). The dogs with leishmaniasis showed increased WBC levels compared with the control group. Similarly, their vitamin D levels were significantly decreased compared with those in the control group (p&lt;0.05). Severely diseased dogs (stage IV leishmaniasis) showed the lowest vitamin D levels, but there were no significant differences between dogs in the various stages of leishmaniasis. The evidence provided by this study indicates that the CVL dogs had low-grade systemic coagulation and fibrinolytic activation, as indicated by elevated MPV, PT, WBC and D-dimer levels, which may be used as a biomarker of low-grade systemic inflammation in CVL.

Ischemic stroke as initial manifestation of systemic lupus erythematosus: A case report and review of the literature.

Stroke is a frequent occurrence among patients suffering from systemic lupus erythematosus (SLE), but it rarely occurs as the initial manifestation of the disease. We here present the case of a 37 year-old patient who developed an acute cerebellar ischemic stroke as initial event of SLE: elevated partial thromboplastin time and ESR, thrombocytopenia, anti-ds-DNA, anti-SSA, anti-JO-1, and the lupus anticoagulant were detected, and the diagnosis of SLE was established. In addition, we reviewed the literature in order to clarify the demographic, clinical, imaging and outcome characteristics of such a presentation, and found 10 similar cases. Most patients were young (age 31.7 ± 8.5 years) and women (8/11, 72.7%). Stroke most often affected the vertebrobasilar territory (7/11, 63.6%). The stroke mechanism was not clearly defined in these cases. Treatment with immunosuppression and anticoagulation was considered to be a reasonable choice for early secondary stroke prevention. The occurrence of ischemic stroke, primarily in the vertebrobasilar system among young patients, especially women, should always raise suspicion for underlying SLE, and prompt diagnostic investigations to confirm or exclude its presence.

Acquired factor VIII deficiency: two case reports and a review of literature

BackgroundAcquired factor VIII (FVIII) deficiency, or acquired hemophilia A (AHA), is a rare autoimmune disorder involving antibody-mediated depletion of coagulation FVIII, leading to severe, life-threatening bleeding. The condition is often associated with other autoimmune disorders, and its treatment involves replacement of FVIII and various modes of immunosuppression. Recently, a few noteworthy therapeutic advances have been made. We present two cases of severe AHA in Chinese women. One of these women developed this disorder in the setting of possible parvovirus B19 infection, which has not yet been reported in association with AHA. Other notable features of her case included paradoxical venous thrombosis and possible association with Sjogren’s syndrome and myositis. The other woman failed to respond to usual first-line therapies despite exhibiting a less severe clinical course, illustrating the varied but potentially stubborn behavior of this disorder.Case 1An 87-year-old woman presented with diffuse ecchymoses, melena, vaginal bleeding. Labs showed hemoglobin (Hgb) nadir of 5.7 mg/dL, elevated partial thromboplastin time (PTT), FVIII level <1%, mixing study consistent with an inhibitor, elevated anti-Sjogren’s-Syndrome-related antigen A antibody, elevated creatinine kinase, and elevated parvovirus IgM and IgG. Imaging of her arm showed diffuse myositis and deep venous thrombosis. After intravenous and oral steroids, her FVIII levels normalized, and her symptoms subsided.Case 2A 59-year-old woman presented with recurrent ecchymoses and hematomas in her extremities. Labs showed Hgb of 11.7 mg/dL, elevated PTT, FVIII level of 3%, and mixing study consistent with an inhibitor. Despite receiving a long course of steroids, several courses of IVIG, and a few courses of Rituximab, her FVIII level remained critically low.ConclusionThe rarity of AHA limits our understanding of this disease and the ability to perform trials to discover optimal therapies. We hope that these case reports and discussion will shed further light on the varied clinical manifestations and natural histories of this disorder to guide better recognition and treatment of AHA.

Case Study of a Complicated Postpartum Recovery Related to Acute Fatty Liver of Pregnancy

Background Acute fatty liver of pregnancy (AFLP) is a fatty acid metabolism disorder that usually occurs when the mother is carrying a male infant and has an associated risk for long‐chain 3‐hydroxyacyl‐coenyme A dehydrogenase (LCHAD) deficiency in the infant. The disease is usually evidenced in the third trimester of pregnancy or postpostpartum but may occur as early as 26 weeks gestation. Researchers have established an AFLP triad: symptoms: nausea/vomiting, jaundice, epigastric pain; laboratory results: renal dysfunction, coagulopathy, liver function abnormalities, hypoglycemia; and complications: renal failure, coagulopathy, ascites, and encephalopathy. Case On Day 2 the woman had a decreased level of consciousness and was “not acting right” according to the nurse. The rapid response team was called, and after a stat head computerized tomography (CT), the woman was transferred to the intensive care unit (ICU). Blood tests at that time revealed low sodium, 124; potassium, 4.8; low chloride, 95; elevated creatinine, 2.3; low glucose, 9; elevated aspartate aminotransferase (AST), 131; elevated alanine transaminase (ALT), 65; elevated alkaline phosphatase, 308; total bilirubin, 9.3; direct bilirubin, 6.1; elevated internationalized normal ratio (INR), 2.6; elevated prothrombin time (PT), 26.4; elevated partial thromboplastin time (PTT), 48.6; elevated ammonia level, 53; low platelets, 52; and low fibrinogen < 50. A physical examination also revealed bilateral scleral icterus with overall jaundice. AFLP was diagnosed, differentiated from hemolysis elevated liver enzymes and low platelets (HELLP) by elevated PT/PTT, INR, and low glucose in addition to the low fibrinogen and elevated ammonia level. The woman also exhibited acute renal failure (ARF) as evidenced by elevated serum creatinine, peripheral edema, and low urine output. Cryoprecipitate and vitamin K were ordered along with serial labs. The woman required intubation and mechanical ventilation due to worsening pulmonary edema. A head CT was ordered due to continued decreased mentation with hepatic encephalopathy. A small subarachnoid hemorrhage (SAH) was noted and neurosurgery and neurology were consulted. A follow‐up magnetic resonance imaging (MRI) was used to further evaluate the SAH and electroencephalogram (EEG) was used to evaluate subclinical seizure activity. The woman was transferred to the neurosurgical ICU for further care and seizure monitoring. The woman remained in status epilepticus with a pentobarbital infusion for 28 days due to encephalopathic state with severe diffuse cerebral dysfunction. Conclusion Interdisciplinary collaboration resulted a full recovery for the woman, and she was discharged on Day 87. Acute fatty liver of pregnancy (AFLP) is a fatty acid metabolism disorder that usually occurs when the mother is carrying a male infant and has an associated risk for long‐chain 3‐hydroxyacyl‐coenyme A dehydrogenase (LCHAD) deficiency in the infant. The disease is usually evidenced in the third trimester of pregnancy or postpostpartum but may occur as early as 26 weeks gestation. Researchers have established an AFLP triad: symptoms: nausea/vomiting, jaundice, epigastric pain; laboratory results: renal dysfunction, coagulopathy, liver function abnormalities, hypoglycemia; and complications: renal failure, coagulopathy, ascites, and encephalopathy. On Day 2 the woman had a decreased level of consciousness and was “not acting right” according to the nurse. The rapid response team was called, and after a stat head computerized tomography (CT), the woman was transferred to the intensive care unit (ICU). Blood tests at that time revealed low sodium, 124; potassium, 4.8; low chloride, 95; elevated creatinine, 2.3; low glucose, 9; elevated aspartate aminotransferase (AST), 131; elevated alanine transaminase (ALT), 65; elevated alkaline phosphatase, 308; total bilirubin, 9.3; direct bilirubin, 6.1; elevated internationalized normal ratio (INR), 2.6; elevated prothrombin time (PT), 26.4; elevated partial thromboplastin time (PTT), 48.6; elevated ammonia level, 53; low platelets, 52; and low fibrinogen < 50. A physical examination also revealed bilateral scleral icterus with overall jaundice. AFLP was diagnosed, differentiated from hemolysis elevated liver enzymes and low platelets (HELLP) by elevated PT/PTT, INR, and low glucose in addition to the low fibrinogen and elevated ammonia level. The woman also exhibited acute renal failure (ARF) as evidenced by elevated serum creatinine, peripheral edema, and low urine output. Cryoprecipitate and vitamin K were ordered along with serial labs. The woman required intubation and mechanical ventilation due to worsening pulmonary edema. A head CT was ordered due to continued decreased mentation with hepatic encephalopathy. A small subarachnoid hemorrhage (SAH) was noted and neurosurgery and neurology were consulted. A follow‐up magnetic resonance imaging (MRI) was used to further evaluate the SAH and electroencephalogram (EEG) was used to evaluate subclinical seizure activity. The woman was transferred to the neurosurgical ICU for further care and seizure monitoring. The woman remained in status epilepticus with a pentobarbital infusion for 28 days due to encephalopathic state with severe diffuse cerebral dysfunction. Interdisciplinary collaboration resulted a full recovery for the woman, and she was discharged on Day 87.

An update on management of pediatric epistaxis

ObjectiveTo evaluate the work-up and treatment of pediatric epistaxis in an outpatient clinical setting, with a focus on the diagnostic utility and associated costs of nasal endoscopy and adjunctive laboratory data. Study designRetrospective, case series. MethodsChildren under 18 years of age seen in an outpatient clinical setting at a tertiary care hospital between 2004 and 2012 for the primary diagnosis of epistaxis were identified. Patient characteristics were analyzed from a statistical and cost perspective. ResultsA total of 175 patients with epistaxis were included. One hundred twenty-two (69.7%) were male, with a mean overall age of 9.1 years (range 5 months to 17.9 years). The duration of bleeding ranged from 0.25 to 84 months (mean 11.5 months). Nasal endoscopy was performed in 123 (70.2%) patients. Three (2.4%) had nasal polyps, and 1 (0.8%) a juvenile nasopharyngeal angiofibroma. The average age of patients with nasal masses was significantly older (16.2 years versus 10.4 years, p=0.008). Of 131 patients with available blood work, laboratory values demonstrated anemia in 27 (20.6%) patients, elevated partial thromboplastin time in 5 (3.8%), and an abnormal platelet function analysis in 1 (0.8%) patient. Those with anemia were statistically younger (p=0.001), than those with either normal labs or abnormal coagulation studies. Epistaxis resolved in 88/135 (65.2%) who had follow-up visits. ConclusionThe majority of pediatric epistaxis cases resolved with nasal mucosa hydration. Nasal endoscopy can be reserved for teenaged patients with epistaxis, and routine laboratory screening may be useful in select cases based on the clinical judgment.

Multifocal subdural hematomas as the presenting sign of acquired hemophilia A: a case report

BackgroundAcquired hemophilia A (AHA) is a rare coagulopathy linked to a variety of etiologies including autoimmune diseases, neoplasms, diabetes, respiratory diseases, and the post-partum state. While bleeding in AHA is often seen in mucocutaneous or intramuscular locations, intracranial and intraspinal bleeds are exceedingly rare.Case presentationWe report an unusual case of spontaneous multifocal subdural hematomas in a 25 year old Asian woman with lupus who presented with headache and backache, and was found to have an elevated partial thromboplastin time (PTT) level and new diagnosis of AHA.ConclusionsSubdural hematomas as the initial sign of AHA are all but unknown in the medical literature. We bring this entity to the attention of the neurology community because lumbar puncture and/or conventional angiogram are often indicated in the work-up of idiopathic multifocal subdural hematomas, but may be dangerous in patients with AHA.

Hematologic Abnormalities and Bleeding in Copperhead Snakebite

Patients with copperhead snakebite tend to have less severe hematologic abnormalities than with other pit viper bites, yet those laboratory studies are routinely ordered. The purpose of this study was to characterize the incidence of abnormal hematologic studies in patients with copperhead bite, and to determine whether these abnormalities are associated with clinically significant bleeding. Using established methodology for retrospective chart review, we performed blinded, dual chart abstraction for all patients who had verified copperhead bite presenting to a tertiary care emergency department from April 2009 to October 2012. Data collected included platelet count, serum fibrinogen, prothrombin time, partial thromboplastin time, predefined clinically significant bleeding, death, and antivenom use. Confidence intervals of proportions were calculated using the Wilson score interval. Ninety-four patients presented with copperhead bite during the 41-month study period. The mean age was 37 years (SD 21 years); 51% (48 of 94) were male. In all, 98% of patients (92 of 94) had at least a single set of the studies performed. Hematologic abnormalities occurred in 27% (95% CI: 0. 21–0.39) of these patients: 4% (4 of 92) had thrombocytopenia (range 96–147 ×109/L); 18% (17 of 92) had hypofibrinogenemia (range 142–212 mg/dL); 5% (5 of 92) had an elevated prothrombin time (range 13.4–14.1 s); and 3% (3 of 92) had an elevated partial thromboplastin time (range 38.5–39.3 s). No clinically significant bleeding or death was observed (0%, 95% CI: 0–0.04). Ninety percent of patients received antivenom therapy. Although a substantial proportion of patients had a measurable hematologic abnormality, no clinically significant bleeding occurred. Routine hematologic tests to detect significant bleeding in all patients with copperhead snakebite and access to antivenom therapy are not warranted. Which patients will benefit from testing, and the role of these tests as prognostic markers of systemic or local tissue symptoms, remains unclear.

DGUOK‐Related Mitochondrial DNA Depletion Syndrome in a Child With an Early Diagnosis of Glycogen Storage Disease

<i>DGUOK</i>‐Related Mitochondrial DNA Depletion Syndrome in a Child With an Early Diagnosis of Glycogen Storage Disease

Rituximab and intravenous immunoglobulin (IVIG) for the management of acquired factor VIII inhibitor in multiple myeloma: case report and review of literature

Acquired factor VIII inhibitor (AFI) is a rare disorder and is even more uncommon in multiple myeloma patients, with only five cases reported in literature. Solid and hematologic malignancies, autoimmune conditions, drugs, and infections are the conditions commonly associated with the development of this condition, with mucocutaneous bleeding being the most common presenting sign. Diagnosis is usually made with the laboratory finding of an elevated partial thromboplastin time aPTT that cannot be corrected by plasma mixing, and further confirmed by low factor VIII activity/antigen levels along with elevated factor VIII inhibitor levels using the Bethesda assay. Treatment is usually based on the clinical picture with factor VIII inhibitor bypass activity (FEIBA) and recombinant factor VIIa (rFVIIa) employed to control acute bleeding; steroids and cyclophosphamide to suppress the inhibitor with Rituximab, in combination with other immunosuppressants in cases not suitable for steroids, and finally wherever possible, to remove the offending drug or control the underlying pathology that might predispose to the development of this condition. This case report highlights the successful management of a myeloma patient who presented with life-threatening hemorrhagic pericardial effusion and hemarthrosis. The patient was treated with FEIBA to control the acute bleeding and then received Rituximab in combination with intravenous immunoglobulin to suppress the AFI.

Postoperative Bleeding after AB0-incompatible Living Donor Kidney Transplantation

Background Since 2007, we have performed 14 AB0-incompatible (AB0i) living kidney transplantations to increase the number of living kidney transplantations. Methods To prevent clotting, donor kidneys were perfused with an HTK/heparin solution with heparin washed out immediately pretransplantation. However, in 4/14 recipients, significant postoperative diffuse hemorrhage occurred with the need for surgical intervention in 3 patients. To analyze the cause of postoperative diffuse bleeding, sequentially before and after opening the graft anastomosis, we prospectively performed coagulation studies: partial thromboplastin time (PTT), thrombin time, thromboplastin time, fibrinogen, antithrombin, d- dimers, plasminogen, and thrombelastography. Results We found no clotting disturbances owing to blood group–specific immunoadsorption. However, 3/4 patients with bleeding complications showed elevated PTT values even 2 hours after opening the anastomosis, which was proven to be a heparin effect by in vitro application of heparinase. Hyperfibrinolysis and disturbances of platelet aggregation were not detected. Because of these results, we lowered the heparin dose administered after donor nephrectomy from initially 10,000–20,000 to 4000 IU resulting in significantly lower PTT values at 2 hours (34.6 ± 4.5 s among patients 6–14 vs 69.0 ± 16.3 s among patients 1–5; P = .012). There were no further bleeding complications. Lowering the heparin dosage had no impact on graft function: serum creatinine at discharge of 1.5 ± 0.1 versus 1.6 ± 0.2 mg/dL. Conclusion Our data indicated that postoperative hemorrhage after AB0i kidney transplantation was associated with the amount of heparin used for graft perfusion after donor nephrectomy. The use of antifibrinolytic agents may be harmful; no hyperfibrinolysis takes place in the AB0i transplant setting.