Sridharan, Meera

Abstract Background Thrombotic microangiopathy (TMA) is a clinicopathologic diagnosis that can be characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia and end-organ damage. Though most patients will present with the hematologic abnormalities of MAHA and thrombocytopenia, there are some that never demonstrate those features and only present with acute renal injury. Here we describe the clinical presentation, laboratory assessment, management, and outcomes of patients with renal-limited TMA (rTMA). Methods After IRB approval, the electronic medical record was searched from 2008-March 2017 for patients managed at our institution with a clinical diagnosis of rTMA supported by renal biopsy. Inclusion criteria were as follows: 1) Presence of TMA on renal biopsy, 2) Absence of MAHA 3) No history of renal transplant prior to diagnosis of TMA. Clinical notes were reviewed to document the physician-determined cause of TMA. If no cause was listed, cause of TMA was based off of labs and clinical observation. Results Thirty-five patients (18 female) met clinical criteria for a diagnosis of rTMA. Median age at time of biopsy was 59 years (range 9 to 87). Creatinine at time of biopsy was 2.4 mg/dL (range 0.55 to 6.4). Evidence of chronic TMA was noted on 17 specimens and an additional 3 had findings of chronic and acute TMA. Ten patients had ADAMTS13 activity performed and all were >10% with negative inhibitor screen (median 66%(26-100)). 24 patients (68.6%) had complement serology assessed. Three patients (12.5%) had low C3 while C4 was normal in 19 patients (79%). One patient in our cohort had complement mutational testing performed with no evidence of a pathogenic variant. Most common etiology of rTMA was medications (28.5%) and underlying rheumatologic disorder (20%)(Table 1). In 6 patients (17%), an identifiable cause was not elucidated. Management of TMA was dependent on underlying etiology of rTMA. Discontinuation or dose adjustment of TMA-causative medications was recommended in 4 patients and 25% of patients had normalization of Cr. Four patients received therapeutic plasma exchange (TPE) for median 5 (2-5) days. Causes of rTMA for those receiving TPE were gemcitabine, bevacizumab, unspecified connective tissue disease, and rTMA due to an unknown cause. 50% of patients were noted to have improvement in Cr with TPE. Antihypertensive medications were used for rTMA secondary to uncontrolled hypertension (n=4) and scleroderma (n=4). 11 patients (31%) were observed or treatment for causative underlying etiology was pursued, while 7 patients were treated with glucocorticoids. Of 6 patients, with no identifiable underlying cause, 4 were treated with observation, 1 was treated with GC, and one was treated with TPE Fourteen patients (38.9%) required dialysis; 6 of these patients were able to discontinue dialysis less than two months after initiation. Three patients (8.3%) with rTMA, respectively due to tacrolimus toxicity, longstanding hypertension, and systemic lupus erythematosus, received a renal transplant, and one additional pt (2.8%) with rTMA due to scleroderma remained on the renal transplant waiting list at time of death. In a median follow-up time of 8.73 months (range 0 to 47.9), 16 patients (44.4%) died. Median time from diagnosis of TMA to death was 12.1 months (range 1.47 to 58.2). No deaths were directly attributable to underlying TMA. Conclusion Renal-limited TMA is a pathologic diagnosis that in our cohort was most likely to medications or underlying rheumatologic conditions. rTMA was managed by treating the underlying disorder or removing the causative medication. Though cause of rTMA was evident in the majority of patients, 17% had no identifiable precipitating factor predisposing to rTMA. Larger studies are required to delineate optimal management and surveillance strategies for these patients. Disclosures No relevant conflicts of interest to declare.

Abstract Background Tunneled central venous catheters have traditionally been used for administration of chemotherapy (chemo) for acute leukemia treatment. Peripherally inserted central catheters (PICC) are increasingly being used, but there is an increased risk of PICC-associated thrombosis (PAT). There is limited information on management of PAT in this subgroup of patients (pt). Methods In this retrospective cohort study we investigated the primary management of PICC related upper extremity venous thrombosis (TB) in pt with hematologic malignancy undergoing chemo at Mayo Clinic Rochester. Eligible pt were 18 years and older, had documentation of PICC placement at our institution, initiation of chemo within a week of PICC placement, and the TB was objectively documented by compression venous ultrasound (CVU). Superficial venous TB (SVT) was defined as TB of subcutaneous veins (basilic and cephalic) and deep venous TB (DVT) defined as TB of brachial, axillary, subclavian, or innominate superior vena cava and internal jugular veins. We retrospectively stratified initial management (IM) into 1) PICC removal alone (PR), 2) PR and therapeutic anticoagulation (AC), 3) AC alone, and 4) conservative management (CM) consisting of symptomatic care and observation. We also investigated factors influencing IM of PAT. Long term outcomes including incidence of pulmonary embolism (PE), post phlebitic syndrome and recurrence of TB were noted. Results Between 2006 and 2012, 190 pt with AML (n=160), MDS or MDS/MF (n=10), or ALL (n=20) met our study criteria. Overall, 40/190 (21.6%) developed PAT: AML n=38, ALL n=1, MDS/MF n=1. SVT occurred in 16/40 (40%) pt and DVT occurred in 24/40 (60%) pt. IM is shown in Table 1. One pt with SVT received AC for 6 weeks as well as PR. In this pt, IM included AC because of proximity of TB to deep veins. 7 pt had a follow up (f/u) CVU within 3 months demonstrating: TB progression (prog, n=1, IM with PR alone but with prog AC was started); TB stability (stab, n=2, both IM with PR alone) and TB resolution/improvement (R/I, n= 4, 2 IM with PR and 2 IM with CM) In the 5 pt with CM, 2 pt had f/u CVU demonstrating improvement, one pt had charted clinical improvement , and 2 pt had no charted clinical f/u. Of DVT pt on AC (n=14), 5 pt completed at least 2 months of AC. Reasons for early cessation (n=9) of AC included thrombocytopenia (tcp, n=4), hematoma (n=1), hematuria (n=1), subarachnoid hemorrhage (n=1), and unknown (n=1). One pt died 2 days after presence of DVT was noted. Two pt initially treated with PR alone developed a second TB with placement of a new PICC on contralateral arm and AC was subsequently initiated (duration: 3 months (n=1), and 8 days (n=1)). 14 pt with DVT had f/u CVU within 3 months which demonstrated prog (n=2), stab (n= 8), or R/I ( n=4) of TB (Table 2). The 2 pt with TB prog subsequently received longer term AC guided by platelet count. In 5 pt with PICC not initially removed, 3 pt had PR after completion of chemo. (1-4 days), one pt had PR at discharge (27 days from TB), and one pt had PICC in place on discharge. One pt with DVT experienced a PE within one year f/u. This pt had initially completed 3 days of AC which was stopped because of tcp. Conclusion In this cohort of patients with PAT, the most common IM consisted of PR, which appeared to result in a low recurrence rate among pt with SVT. In pt with DVT, the role of AC remains to be defined given the abbreviated course of AC in most pt. Though, the lack of CVU followup in all pt limits conclusions, there appeared to be a low rate of symptomatic prog. Initiation of AC was largely guided by platelet count and degree of occlusive symptoms. Thrombocytopenia was also the most commonly cited reason for discontinuing AC. Close clinical follow up aided by the use of CVU was integral to ensure that PAT did not lead to further adverse events. Disclosures: No relevant conflicts of interest to declare.

Abstract Introduction: Gardner-Diamond Syndrome (GDS), also known as psychogenic purpura, is a rare disorder characterized by unexplained recurrent painful bruising typically arising after physical and/or psycho-emotional stress. Classically ecchymoses (ecch) spontaneously appear and are associated with a prodrome of warmth and pain at the ecch sites. Prior GDS reports are limited to single cases or small series. Aims:To characterize presentation, natural history, management and long term outcomes (LTO) of GDS. Methods: In this retrospective study, after IRB approval, patients (pt) with GDS, encountered between 1976 and 2016, were identified from within Mayo Clinic Rochester clinical databases. Medical records of consenting pts were reviewed. Results: 75 females (ages 16-69 years (yr)) and 2 males (46-65 yr) met our study criteria. Pt presented 3.2 yrs (range 0-27) after onset of initial symptoms (sym). 52 pt (67.5%) had an antecedent history of physical abuse (n=2), trauma (n=12), an emotional event (n=13), surgery (n=11), or infection (n=3). Prodromal sensations prior to appearance of ecch in 55 pts (71.4%) were described as itching (n=15), burning (n=19), stinging (n=11), and/or pain (n=44). Other localized sym after appearance of ecch included swelling (n=46) and pain (n=67). Maximum size of ecch ranged from >0 and ≤5 cm (n=26), ≥6 and ≤ 10 cm (n=14), and >10 cm (n=13) and not described in 24 pts Systemic sym at time of ecch, reported in 49 pts, included malaise (n=26), myalgia (n=21), headaches (n=19), fevers (n=15), and abdominal pain (n=10). 50 (65%) of pts' lesions were isolated to arms and legs, while 27 (35%) had trunk and head involvement in addition to extremity involvement. Ecch duration varied: 0-7 days (n=14), 1 week-1 month (n=31), or >1 month (n=5) and not described in 27 pts. Complete blood count was normal (nl) in 84% (64/76) of pts tested; anemia was the most common abnormality. PT, APTT, VWF, and Factor XIII screen were nl in 100% (67/67), 98.4% (63/64), 97.9% (46/47), and 100 % (30/30) of pts respectively. Platelet aggregation studies were nl in 83% (25/30) with abnormalities attributed to drug effect. Bleeding (bld) scores (ISTH BAT), calculated with exclusion of cutaneous (cut) manifestations in scoring, were: 0 (n=48), 1 (n=12), 2 (n=9), 4 (n=2), 5-6 (n=2), 7 (n=2), and 9 (n=2). 21 pts had testing with subcut injections of autologous red cells (SCIAR) with 9 positive and 2 equivocal. 28 pts had skin biopsies with the most common finding being subcut hemorrhages. 45 pts (58.4%) underwent psychiatric (psych) evaluations and 7 (15%) pts were found not to have a psych dx. 42 pts had a psych dx including depression (n=23), hysterical personality (n=8), anxiety (n=2), personality disorder (n=2), psych other (n=7). Of these pts, 4 did not undergo further psych eval given prior dx. 42 pts had a history of a neurological dx including headaches (n=34), paresthesias (n=10), and seizures (n=7). Additional pharmacological treatments (pharmt) were recommended for 30 pts: antidepressants (n=4), antihistamines (n=13), anti-inflammatory/immunosuppressants (n=11), or hormonal (n=2) medications. 47 pts were treated with observation and/or counseling alone to address psychological stressors. 28 pts had follow-up (fu) at least 1 yr (1 to 34 yrs) after the initial visit. 13 of these pts had no mention of recurrence during fu while 15 pts had continued recurrence. Of those with recurrence, 7 pts continued to seek fu for GDS. Conclusion: In this large clinical cohort of GDS pts we confirm and expand on known clinical findings of GDS. Majority of pts had fairly benign disease (dz) manifestations; however, in a subset, a negative impact on pt quality of life was noted due mainly to persistent/recurrent pain. Refractory dz was mostly associated with ongoing/ recurrent stressors. The relatively low bld scores, together with laboratory assessments, support that GDS is primarily a dermal rather than a systemic bld diathesis. SCIAR did not provide additional value in dx. CBC, PT, APTT & VWF testing should be performed, and platelet testing considered, to rule out other hemostatic dz. Addressing stressors was the most effective treatment for pts, however pharmt was given for refractory dz. Though our study provides new insights regarding dx, therapy and LTO, future work investigating the pathophysiology leading to the hemostatic abnormalities in GDS would be valuable. Disclosures No relevant conflicts of interest to declare.

AbstractObjectivesDescribe the clinical presentation, treatment, and outcomes of postsurgical thrombotic microangiopathy (TMA).MethodsIn this retrospective study, records of individuals diagnosed with TMA developing within 30 days of a surgical procedure at Mayo Clinic from 2000 to 2016 were reviewed. Available literature regarding postsurgical TMA was comparatively reviewed.ResultsTwenty patients were diagnosed with TMA developing within 30 (median 6.5, range (1‐28)) days) following a procedure. Preceding procedures included orthopedic (n = 4), vascular (n = 4), abdominal (n = 8), thoracic (n = 2), and other (n = 2). Review of the literature identified 65 patients with postsurgical TMA and cardiovascular procedures were the most common preceding surgery. The majority of patients in the current cohort and literature were treated with therapeutic plasma exchange (TPE). Among the evaluable patients in the current cohort, 100% demonstrated response to TPE; however, 25% required the addition of other therapy including eculizumab to maintain a response 80% of patients in the literature demonstrated a response to TPE.ConclusionsAlthough rare, early recognition and treatment of postsurgical TMA can lead to good outcomes. More research is necessary to determine the underlying pathophysiology and optimal treatment for postsurgical TMA.