An atypical presentation of endometrial cancer as angina secondary to critically low hemoglobin and iron deficiency associated pancytopenia: A case report.

Endometrial cancer is the most common type of gynaecological cancer in high-income countries. Abnormal uterine bleeding (AUB) is the most common symptom of endometrial cancer; however, patients can often present in an atypical fashion. This case is an example of an atypical presentation of endometrial cancer, with angina secondary to severe iron deficiency anemia, and a rare example of pancytopenia secondary to iron deficiency. A 46-year-old nulliparous woman with no past medical history presented to the emergency department with acute chest pain. All her vitals were normal. The ECG showed T-wave inversion with a negative serum troponin. She had obvious pallor but appeared well. She had a critical hemoglobin of 1.9 g/dL and severe iron deficiency with a plasma iron level of <2 µg/L. In the 6 months leading up to her presentation, she had heavy and prolonged menstruation of up to 10 days. She received a total of 6 units of packed red blood cells and an iron infusion. Her chest pain resolved, and her pancytopenia corrected following replenishment of iron stores. She underwent a laparoscopic total hysterectomy, bilateral salpingo-oophorectomy for stage 1b, grade 2 endometroid adenocarcinoma. This is one of the lowest hemoglobin levels recorded in a hemodynamically stable patient with endometrial cancer, and the only case report of iron deficiency induced pancytopenia secondary to abnormal uterine bleeding. This case is a reminder that female patients with angina should have their hemoglobin checked, and patients with anemia should have a thorough review of their gynaecological history.

Outcomes and anticoagulation use for elderly patients that present with an acute hip fracture: multi-centre, retrospective analysis.

BACKGROUND: Hip fractures are a common problem and corrective surgery is recommended within 24 h. However, most peri-operative direct oral anticoagulant (DOAC) guidelines suggest a washout period of 48 h before major surgery. There are limited data on utility of drug levels. AIM: To investigate the effect of DOAC therapy on time to surgery and patient outcomes, and to explore the impact of different pre-operative protocols on surgical delay. METHODS: A multi-centre, retrospective analysis of all adult patients that presented with acute hip fracture at three tertiary hospitals in Perth, Western Australia, was performed. Data were collated from the West Australian hip fracture registry and electronic records. Time to theatre, DOAC levels, bleeding and transfusion rates were compared between sites. RESULTS: Of 1240 hip fracture patients, 146 (11.9%) were on anticoagulation, with more patients taking a DOAC than warfarin. The time to surgery was significantly longer for those on a DOAC compared with those on warfarin (P = 0.003). There was no difference in bleeding, transfusion requirement or 30-day mortality in patients taking a DOAC compared to those on warfarin. Fifty-eight (70.7%) patients had a DOAC level prior to surgery. Of 25 patients who had a level performed within 12 h of presentation, 13 (52%) had a result of ≤50 ng/mL. Outcomes were similar between sites. CONCLUSION: People on DOAC treatment had a significant delay before corrective surgery compared with those on warfarin. The frequent finding of early DOAC levels <50 ng/mL suggests this delay may be unnecessary in a significant proportion of patients.

Long-term safety and sustained efficacy for up to 5 years of treatment with recombinant factor IX Fc fusion protein in subjects with haemophilia B: Results from the B-YOND extension study.

INTRODUCTION: Recombinant factor IX Fc fusion protein (rFIXFc) has demonstrated efficacy for treatment of haemophilia B in the Phase 3 B-LONG and Kids B-LONG studies. However, long-term rFIXFc safety and efficacy data have not yet been reported. AIM: To report long-term rFIXFc safety and efficacy in subjects with haemophilia B. METHODS: B-YOND (NCT01425723) was an open-label extension for eligibl previously treated subjects who completed B-LONG or Kids B-LONG. Subjects received ≥1 treatment regimen: weekly prophylaxis (WP), individualized interval prophylaxis (IP), modified prophylaxis or episodic treatment. Subjects could switch regimens at any time. The primary endpoint was inhibitor development. RESULTS: Ninety-three subjects from B-LONG and 27 from Kids B-LONG (aged 3-63 years) were enrolled. Most subjects received WP (B-LONG: n = 51; Kids B-LONG: n = 23). For subjects from B-LONG, median (range) treatment duration was 4.0 (0.3-5.4) years and median (range) number of exposure days (EDs) was 146 (8-462) EDs. Corresponding values for paediatric subjects were 2.6 (0.2-3.9) years and 132 (50-256) EDs. No inhibitors were observed (0 per 1000 subject-years; 95% confidence interval, 0-8.9) and the overall rFIXFc safety profile was consistent with prior studies. Annualized bleed rates remained low and extended-dosing intervals were maintained for most subjects. Median dosing interval for the IP group was approximately 14 days for adults and adolescents (n = 31) and 10 days for paediatric subjects (n = 5). CONCLUSIONS: B-YOND results confirm the long-term (up to 5 years, with cumulative duration up to 6.5 years) well-characterized safety and efficacy of rFIXFc treatment for haemophilia B.

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A.

Recombinant VIII (rVIII)-SingleChain is a novel B-domain-truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927.

Undiagnosed myeloproliferative disease in cases of intra-abdominal thrombosis: the utility of the JAK2 617F mutation.

BACKGROUND & AIMS: Extrahepatic portal vein thrombosis and Budd-Chiari syndrome frequently result from multiple concurrent factors such as cirrhosis, intra-abdominal sepsis, procoagulant states, and underlying myeloproliferative disorders (MPDs). The JAK2 V617F mutation is a point mutation in the Janus kinase 2 (JAK2) tyrosine kinase that is variably present in MPDs. The incidence depends on the subclassification of the MPDs and the sensitivity of the assay used. This case series aimed to illustrate the diagnostic utility of JAK2 V617F mutation in atypical cases of MPD that otherwise may not have met traditional diagnostic criteria. METHODS: Granulocytic DNA was obtained and real-time polymerase chain reaction was performed using allele-specific primer and probe to provide a quantitative expression of the V617F mutation. RESULTS: The JAK2 V617F point mutation was found in 3 patients with extrahepatic portal vein thrombosis who had multiple thrombotic events but did not fulfill the traditional diagnostic criteria for MPDs. CONCLUSIONS: A sensitive assay for the JAK2 V617F mutation has the potential to diagnose atypical MPDs in multiple undiagnosed cases of intra-abdominal thrombosis and therefore alter the management and prognosis of these patients.

A case report of transfusion-related acute lung injury during plasma exchange therapy for thrombotic thrombocytopenia purpura.

Transfusion-related acute lung injury (TRALI) is a transfusion reaction that is often under recognized and underreported. Implications for diagnosis not only influence treatment considerations but also extend to donor selection, donor deferral and ultimately the safety of the final blood product. We report a case of a previously well 19-year-old female who presented a one week history of flu-like symptoms and mucosal bleeding. Laboratory results confirmed the diagnosis of thrombotic thrombocytopaenia purpura (TTP) and she was commenced on plasma exchange. During her second day of plasma exchange, she developed dyspnoea and rigors. Examination and investigation findings were consistent with a clinical diagnosis of TRALI. Granulocytes immunofluorescent test (GIFT - flow cytometry) was performed and cross reactivity was demonstrated between the patient's granulocytes and plasma from one of the nine donor fresh frozen plasma (FFP) packs. She made a full recovery. TRALIa accounts for 7% of all adverse events reported in the Serious Hazards of Transfusion (SHOT) database and has a mortality rate between 5-25%. Apheresis patients are a particularly vulnerable group of patients where clinical recognition and rapid laboratory confirmation of TRALI is imperative to minimize the risk of further patient exposure to donor granulocyte or human leukocyte antigen (HLA) antibodies. The provision of plasma from male donors may additionally reduce exposure. On a wider scale, rapid donor identification and deferral maintains the safety of the national blood supply.

Quantitative determination of JAK2 V617F by TaqMan: An absolute measure of averaged copies per cell that may be associated with the different types of myeloproliferative disorders.

We report a novel TaqMan assay for JAK2 V617F that measures averaged copies per cell in absolute terms, as opposed to a ratio of mutant to wild-type alleles. Measurements were obtained by comparing the JAK2 V617F signal generated by the test samples to that generated by a set of external plasmid standards containing the sequence of interest. Specificity of the assay was demonstrated above 36 cycles of amplification, and endpoint titration experiments indicated sensitivity down to 0.05% clinical dilutions. The test measured linearly over a wide logarithmic range and exhibited good reproducibility. Combination of this assay with another TaqMan method for determining cell number allowed identification of 14 cases of myeloproliferative disease with greater than two copies per cell. Mutational frequency was 68% among polycythemia vera (n=44), 59% (n=37) among essential thrombocythemia and 46% (n=13) among idiopathic myelofibrosis. Levels of the mutation were significantly higher in polycythemia vera compared with essential thrombocythemia (P=0.0005) and correlated with the following jointly significant variables at diagnosis: PRV-1, hemoglobin, white cell count, neutrophil count, and red cell count, using multiple regression analyses (P=0.015). This method should be useful for assessing the relationship of gene dose to phenotype and possibly for monitoring therapy.