Ashrani, Aneel A.

AbstractBackgroundFactor XI (FXI) deficiency (hemophilia C [HEM‐C]) is a bleeding disorder with unpredictable severity that correlates poorly with FXI coagulation activity (FXI:C). It poses a perioperative hemostatic management challenge. For US patients with severe disease, fresh frozen plasma (FFP) or, in current use, thawed plasma is the most readily available option but comes with risk of volume overload. We report our experience of using therapeutic plasma exchange (TPE) as an alternative perioperative management strategy.MethodsA retrospective review of all HEM‐C patients who underwent surgical procedures. Data were collected, including demographics, bleeding history, surgical site, perioperative hemostatic intervention, and outcome.ResultsBetween July 1997 and September 2014, 28 HEM‐C patients (12 men) were identified, 4 with severe disease (FXI:C <2% or excessive bleeding). Nineteen patients underwent 91 invasive procedures. For nearly 60% of the procedures, no periprocedural hemostatic intervention was provided; before 4 procedures (3 patients), 1 plasma volume TPE preoperatively with FFP was administered. Patient 1, a 28‐year‐old woman (FXI:C, 35%) with a history of excessive surgical bleeding, underwent 2 TPE procedures before laparoscopic pelvic biopsy and subsequent abdominal hysterectomy with salpingo‐oophorectomy that increased her FXI:C to 48%. Patient 2, a 79‐year‐old man (FXI:C, <2%), had TPE before total hip arthroplasty, increasing his FXI:C to 24%. Patient 3, a 59‐year‐old man (FXI:C, <2%), had TPE before prostate laser enucleation, increasing his FXI:C to 46%. Patients 1 and 3 had mild reactions during TPE; no patient had evidence of volume overload. All patients had adequate intraoperative surgical hemostatic outcomes.ConclusionTPE is an effective alternative presurgical hemostatic intervention in HEM‐C with potentially lower risk of circulatory volume overload.

IntroductionHaemostatic assessments of patients with von Willebrand disease (VWD) who undergo total knee arthroplasty (TKA) and total hip arthroplasty (THA) have mainly relied on subjective parameters.AimsTo compare objective haemostatic outcomes of TKA/THA in VWD patients and controls without bleeding disorders.MethodsWe retrospectively analysed haemostatic outcomes in VWD patients undergoing TKA/THA from 1993 to 2011 and compared them with two matched controls per operation. Using one‐way analysis of variance, we tested the effect of VWD on bleeding risk after TKA and THA.ResultsTwelve VWD patients (6 type 1, 3 type 2M, 1 each of types 2A/2B/3) undergoing 19 operations (12 TKA, 7 THA) were matched to 38 controls. One (5%) of 19 operations in VWD patients and none of the control operations met clinical criteria for major bleeding. Baseline and postoperative day 1 haemoglobin levels, postoperative blood loss, transfused red blood cells (RBCs) and mean hospitalization days were not significantly different. More VWD patients than controls received RBC transfusions [12 (63%) vs. 12 (32%)]. Only 9 (47%) VWD patients vs. 38 (100%) controls received pharmacologic VTE prophylaxis. No postoperative symptomatic VTE occurred in either group.ConclusionIn this largest, single‐institutional study, von Willebrand factor replacement based on daily levels resulted in low frequency of major bleeding in VWD patients after TKA/THA. RBC transfusion was more frequent compared with matched controls, but other objective measures of haemostasis were similar. Lack of sufficient details in published reports precluded comparison of haemostatic outcomes.

Key Points VTE recurrence risk in patients with cancer can be stratified by cancer type, stage, stage progression, and presence of leg paresis. Patients with cancer at high VTE recurrence risk should be considered for secondary prophylaxis.

Objective Diffuse alveolar hemorrhage (DAH) is an uncommon complication of primary antiphospholipid syndrome (APS). We aimed to describe the clinical characteristics, treatment, and outcomes of primary APS–associated DAH in a single center. Methods We conducted a retrospective review of all adults with primary APS–associated DAH evaluated at Mayo Clinic over a 15‐year period. DAH was defined as bilateral pulmonary infiltrates and bronchoalveolar lavage (BAL) fluid documenting progressively bloody returns and/or the presence of >20% hemosiderin‐laden macrophages. Patients with other causes of DAH were excluded. Results Eighteen patients were identified (median age 43 years). Capillaritis was present in surgical lung biopsy samples of 3 patients. BAL differential cell counts revealed predominantly neutrophils. All patients were treated initially with glucocorticoids. Cyclophosphamide (CYC) was used in 8 patients; complete remission was achieved in 3 patients treated with CYC alone and in 1 patient receiving combination therapy with rituximab (RTX). RTX was used in 9 patients; 2 patients achieved remission with RTX alone, whereas 3 patients required combination therapy with CYC or mycophenolate mofetil (MMF). No patient achieved complete remission while receiving single therapy with MMF, azathioprine, or plasma exchange. Intravenous gamma globulin therapy was administered in 5 patients; no patient achieved control of the disease. Six patients died, all because of complications related to uncontrolled DAH or its therapy. Conclusion We present the largest case series of primary APS–associated DAH reported in the literature. DAH carries a very poor prognosis and therapeutic options are limited. Immunosuppression with either CYC or RTX is associated with the highest likelihood of remission induction and should be considered early.

Objectives To provide nursing home ( NH )‐specific estimates to assess whether venous thromboembolism ( VTE ) risk factors identified for the general population apply to NH residents. Design Population‐based case–control study. Setting O lmsted C ounty, M innesota. Participants All county residents with symptomatic objectively diagnosed incident VTE while resident in a NH from 1988 through 2000 (N = 182) and two age‐, sex‐, calendar‐year‐matched non‐ VTE O lmsted C ounty NH residents per case (N = 364). Measurements Provider‐linked medical records were reviewed to obtain information on active malignancy and recent hospitalization, surgery, trauma, or fracture as of index date (case's VTE date; respective provider registration date for controls). Risk factor prevalence and VTE ‐associated odds ratios ( OR ) were estimated and compared with previously obtained data for all O lmsted C ounty residents from 1988 through 2000. For analyses, both groups were limited to individuals aged 65 and older. Results In NH residents, active malignancy, recent hospitalization, and recent surgery significantly increased VTE risk, but the magnitude of risk appeared much lower than general population estimates (e.g., for major surgery, OR = 2.5, 95% confidence interval ( CI ) = 1.4–4.3 for NH residents vs OR = 11, 95% CI = 7.0–17 for general population). In general, the prevalence of all evaluated VTE risk factors appeared much higher in NH controls than in general population controls. Thromboprophylaxis rates appeared higher for NH cases and controls than in the general population; disconcertingly, 47% of NH cases received prophylaxis. Conclusion Although general population VTE risk factors (active cancer and recent hospitalization or surgery) can identify NH residents at higher risk for VTE , these exposures do not adequately stratify VTE risk for thromboprophylaxis recommendations. Further research into NH ‐specific risk factors and prophylaxis effectiveness is required.

We report the clinical presentation and laboratory findings of a 69-year-old man with fragile X-associated tremor ataxia syndrome (FXTAS), a progressive neurodegenerative disorder, who was noted to have monoclonal gammopathy of undetermined significance (MGUS), a plasma cell proliferative disorder and a precursor disease of multiple myeloma. Both MGUS and FXTAS are associated with microRNA (miRNA) dysregulation. We speculate that individuals with FXTAS may be predisposed to MGUS and further studies are warranted regarding this association.