Presentation of concurrent thrombotic thrombocytopenic purpura and Graves' disease.

Thrombotic thrombocytopenic purpura (TTP) is a type of thrombotic microangiopathy caused by deficient activity of ADAMTS13 that most commonly occurs secondary to an acquired autoantibody. There are limited data on the association between TTP and autoimmune thyroid disease. We present a case of acquired TTP in the setting of thyrotoxicosis from Graves' disease. Our patient improved with standard treatment of both TTP and thyrotoxicosis. A retrospective review of patients with TTP at our institution demonstrated that 32% had another autoimmune disorder, highlighting the concept of polyautoimmunity. These findings suggest an association between TTP and uncontrolled autoimmune disease. In patients with newly diagnosed TTP, physicians should evaluate for other autoimmune diseases and check thyroid function tests.

Factor Xa inhibitors versus low molecular weight heparin for the treatment of cancer associated venous thromboembolism; A meta-analysis of randomized controlled trials and non-randomized studies.

INTRODUCTION: We compared the safety and efficacy of Xa-inhibitors to LMWH for treatment of venous thromboembolism in mixed and gastrointestinal cancer cohorts (CA-VTE). METHODS: A systematic search identified RCTs and non-randomized studies (NRS) comparing Xa-inhibitors to LMWH for treating CA-VTE. Relative risks were computed. Certainty was assessed using the GRADE approach. RESULTS: Xa-inhibitors reduced the risk of recurrent VTE (RR0.64;0.49-0.84) and NRS (RR0.74;0.60-0.92;Moderate-Low Certainty). There was no significant difference in recurrent PE in RCTs (RR0.72;0.50-1.02) and NRS (1.43;0.65-3.12;Low-Very Low Certainty). Xa-inhibitors increased the risk of overall bleeding events in RCTs (RR1.45;1.05-2.01) and NRS (RR1.72;1.42-2.08;Moderate-Low Certainty), and the risk of major bleeding events in NRS (RR1.56;1.17-2.07), but not in RCTs (RR1.33;0.94-1.89; Low-Very Low Certainty). Similar results were detected in gastrointestinal cancer patients. CONCLUSION: Xa-inhibitors may reduce the risk of recurrent VTE, but not recurrent PE compared to LMWH. A higher overall bleeding risk, and a questionably higher major bleeding risk was found with Xa-inhibitor use.

Soluble interleukin-2 receptor (sIL-2r) level is a limited test for the diagnosis of adult secondary hemophagocytic lymphohistiocytosis.

BACKGROUND: Soluble interleukin-2 receptor (sIL-2r) level is used as a diagnostic tool in hemophagocytic lymphohistiocytosis (HLH). However, evidence supporting its use among adults is inadequate. OBJECTIVE AND METHODS: We conducted a retrospective study to assess the performance characteristics of sIL-2r for the diagnosis of adult HLH. RESULTS: One hundred thirty-two adults with sIL-2r levels sent for evaluation of HLH over a ten-year period were included. Sixty-five (49%) met criteria for HLH. Mean sIL-2r was significantly higher among patients with HLH relative to all patients without HLH (12942U/ml vs. 6308 U/mL, P = .00311). However, when comparing mean sIL-2r in the HLH group to those in the non-HLH group with primary diagnoses of hematologic malignancy (8911 U/mL), sepsis (7127 U/mL), and rheumatologic disease (4624 U/mL), no significant differences were found (P = .241, P = .178, and P = .0607, respectively). There was only weak correlation between sIL-2r and diagnosis of HLH (r = .253). The standard cutoff sIL-2r > 2400 U/ml yielded a sensitivity of 89.2% and specificity of 38.8%. The area under the curve for the corresponding receiver-operator curve was 0.691, consistent with a poor discriminating ability for the diagnosis of HLH. CONCLUSIONS: sIL-2r is a limited test for the diagnosis of adult secondary HLH, and its role in this setting should be reevaluated.

The utility of thrombophilia testing in patients with newly diagnosed portal vein thrombosis.

: Thrombophilia testing is frequently performed in both seemingly provoked and unprovoked portal vein thrombosis (PVT), yet the clinical implications of these expensive laboratory tests are unknown. We investigated the frequency of clinical management changes in patients with newly diagnosed PVT. This is a retrospective analysis of adult patients with a newly diagnosed PVT at a single institution. The primary outcome is change in clinical management, defined as documented change in choice, dose, or duration of anticoagulation, future thromboprophylaxis, or counseling of asymptomatic family members. Five-hundred and forty-four patients with PVT were identified, 438 (80.5%) of whom had an identifiable pretesting provoking factor, most commonly cirrhosis (39.2%). Two-hundred ninety-one patients (53.5%) had at least one hypercoagulable laboratory test performed. The most frequently positive test was PAI-1 polymorphism, followed by elevated homocysteine and MTHFR mutational analysis. However, the only test that was frequently positive and consistently altered management was JAK2 mutational analysis (15.3%). Factor V Leiden was commonly positive but rarely changed clinical decision-making (1.5%), as was flow cytometric testing for paroxysmal nocturnal hemoglobinuria (0.8%), and antiphospholipid antibodies (0.7%). Patients with cirrhosis rarely had thrombophilia testing results that were clinically significant. A rough cost estimate was dramatically reduced from $231 000 to $76 000 if only clinically meaningful tests were employed in the hypercoagulable work-up. These results highlight the need for focused thrombophilia testing in patients with PVT.

The efficacy and safety of direct oral anticoagulants in noncirrhotic portal vein thrombosis.

Guidelines currently favor vitamin K antagonists or low-molecular-weight heparins for treatment of noncirrhotic portal vein thrombosis (ncPVT). Use of direct oral anticoagulants (DOACs) in PVT has been met with concern because of the lack of data. We conducted a retrospective study to investigate the efficacy and safety of DOACs for the treatment of ncPVT, and to compare them with standard therapies: 330 patients with ncPVT, followed-up for a mean 41.6 months, received warfarin (n = 108), enoxaparin (n = 70), rivaroxaban (n = 65), apixaban (n = 20), dabigatran (n = 8), fondaparinux (n = 2), or no anticoagulation (n = 57). The primary outcome was complete radiographic resolution (CRR) of PVT. Secondary outcomes included recanalization of occlusive PVT, cavernous transformation of the PV, development of chronic portal hypertensive symptoms (cPHS), and major bleeding. DOACs were associated with the highest CRR rates (dabigatran, 6/8 [75%]; apixaban, 13/20 [65%]; rivaroxaban, 42/65 [65%]). Enoxaparin was associated with a CRR rate similar to that of the DOACs (40/70 = 57%). Warfarin was associated with worse outcomes in this regard (CRR rate, 31% [33/108]; hazard ratio [HR] DOACs:warfarin, 2.91; 95% confidence interval [CI], 1.87-4.52; P < .0001). DOACs were associated with recanalization rates similar to enoxaparin and greater than warfarin (HR DOACs:warfarin, 3.45; 95% CI, 1.93-6.18; P < .0001). DOACs were associated with lower rates of cPHS, although this did not attain significance (DOACs, 8/93 [9%]; enoxaparin, 13/70 [19%]; warfarin, 31/108 [29%]). DOACs were associated with less major bleeding relative to warfarin (HR DOACs:warfarin, 0.20; 95% CI, 0.05-0.86; P = .0307). Patients harboring JAK2V617F, those with no evident predisposing factor for PVT, and those with occlusive thrombus demonstrated worse outcomes. DOACs appear effective and safe for the treatment of ncPVT.

Hemophagocytic Lymphohistiocytosis Due to Primary HHV-8 Infection in a Liver Transplant Recipient.

Human herpesvirus-8 (HHV-8) remains best known as an oncogenic virus, but nonneoplastic disease manifestations, such as bone marrow failure or hemophagocytic lymphohistiocytosis (HLH) have gained greater recognition in recent years. In organ transplantation, HHV-8 infection commonly occurs with reactivation of latent virus among recipients from endemic regions of the world or due to transmission from the organ donor. We describe a case of HHV-8-associated HLH in a liver transplant recipient at increased risk for primary infection. Our case highlights the risk of non-donor-derived, posttransplant primary HHV-8 infection, and demonstrates that HLH can be a life-threatening complication of this infection.

Multiple myeloma in World Trade Center responders: a case series.

OBJECTIVES: We report on cases of multiple myeloma (MM) observed in World Trade Center (WTC) responders registered in the WTC Medical Program. METHODS: Possible cases of MM diagnosed between September 11, 2001, and September 10, 2007, in responders were confirmed if they met the World Health Organization and Mayo Clinic diagnostic criteria. RESULTS: Among 28,252 responders of known sex and age, eight cases of MM were observed (6.8 expected). Four of these cases were observed in responders younger than 45 years at the time of diagnosis (1.2 expected). A slight deficit of MM cases was observed in responders older than 45 years (4 observed, 5.6 expected). CONCLUSION: In this case series, we observe an unusual number of MM cases in WTC responders under 45 years. This finding underscores the importance of maintaining surveillance for cancer and other emerging diseases in this highly exposed population.

Autoimmune disease is a risk factor for the development of non-Hodgkin's lymphoma.

OBJECTIVE: To investigate the relationship of prior autoimmune disease to the development of non-Hodgkin's lymphoma (NHL). METHODS: Patients with NHL (n = 278) seen from 1993 to 2002 were compared with a group of patients with other hematological disorders (controls, n = 317) seen at the same time. All patients were questioned about prior autoimmune disease. Comparisons between NHL patients and controls were based on analysis of a 2 2 table of counts using Fisher's exact test. Analysis of the effect of autoimmune disease on NHL status, controlling for other risk factors, was performed using logistic regression. RESULTS: Thirty-six (13%) NHL patients had a prior autoimmune disease compared to 5% of controls (p = 0.001). Sixty-nine percent of NHL patients with a prior autoimmune disease were female compared to 43% without a prior autoimmune disease, and this was similar in control patients, 69% and 48%, respectively. Twenty percent of all women with NHL had a history of autoimmune disease compared to 7% of women in the control group (p = 0.001). Nineteen of the NHL patients with autoimmune disease (56%) received immunosuppressive treatment compared to 5 (38%) in the controls. CONCLUSION: Autoimmune disease may account in part for the increase in NHL, especially in women.

Primary splenic lymphoma: report of 10 cases using the REAL classification.

Primary splenic lymphoma (PSL) is rare with a reported incidence of less than 1%. Diffuse large cell pathology has been reported in 22-33% of the cases and is felt to have a poor outcome. We report our experience in patients with PSL seen at Mount Sinai Medical Center during the years 1994-1999. Our objective was to evaluate staging (using the Ahmann and Kehoe criteria), prognosis using the International Prognostic Index (IPI), and pathology using the Revised European-American Lymphoma Classification (REAL) classification. Ten patients were identified. Eight of the 10 patients had diffuse large cell lymphoma (DLCL). Using the IPI, four patients were categorized as low risk, three as low/intermediate risk, and three as high risk. The only two deaths occurred in the high-risk group. Lymph node involvement beyond the splenic hilum seen by imaging studies represents an advanced non-Hodgkin's lymphoma and should be included no longer in the staging of PSL. Nine of the 10 underwent a splenectomy. Eight of the nine patients received chemotherapy following splenectomy. Seven of the nine patients remained in remission from 1 to 19 years. Splenectomy followed by combination chemotherapy, results in excellent long-term survival in PSL.

Non-Hodgkin's lymphoma in patients 70 years of age or older: factors associated with survival.

The incidence of non-Hodgkin's lymphoma (NHL) has increased dramatically especially in persons over 60 years of age. We reviewed our experience in patients with NHL who were 70 years of age or older and seen between 1992 and 1998 in an effort to find any unique risk factors in this age group. There were 64 patients. Twenty-five had indolent disease and 38 had aggressive disease. The majority of patients with indolent lymphoma presented with nodal disease and were more likely to have bone marrow involvement. In contrast, 71% of patients with aggressive lymphoma presented with extra-nodal disease. Five of seven (71%) patients with indolent and 22 of 29 (76%) with aggressive NHL who received an Adriamycin containing regimen as first line therapy achieved a complete response. The International Prognostic Index (IPI) was a strong predictor of both survival (P<001) and response (P=007) for the group as a whole. The IPI accurately predicted the survival of patients with aggressive NHL (P=026). This was not the case with indolent lymphomas. This study suggests that elderly patients with NHL are more likely to have aggressive disease, a diffuse pathology and an extra-nodal presentation.