Enzyme replacement therapy leading to improvement in myeloma indices in a patient with concomitant Gaucher disease.

Patients with Gaucher disease (GD) have been shown previously to carry an increased risk for cancer, most commonly multiple myeloma (MM). It is currently unknown whether treatment for GD has an effect on the prevention or amelioration of MM. We present the case of a 41-year-old patient simultaneously diagnosed with GD and smouldering MM. Enzyme replacement therapy with Velaglucerase-alfa significantly improved myeloma indices.

Placental Pathological Findings following Adjusting Enoxaparin Dosage in Thrombophilic Women: Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: Randomized trials showed no improvement in pregnancy outcomes with the use of low molecular weight heparin (LMWH) to prevent placenta-mediated pregnancy complications (PMPCs) among thrombophilic women. However, the effect of treatment on placental findings was not examined. We aimed to examine the occurrence of placental vascular lesions in thrombophilic women treated with LMWH dose adjusted according to anti-factor Xa compared with a fixed dose. STUDY DESIGN: This study was a secondary analysis of a randomized trial designed to examine whether LMWH dose adjusted according to anti-factor Xa levels compared with a fixed dose would reduce the risk of PMPC. Eligible women were randomly allocated in a 1:1 ratio to either a fixed dose of 40 mg daily LMWH (fixed dose group) or adjusted dose according to anti-factor Xa levels (adjusted dose group). Placentas were examined by the same perinatal pathologist who was blinded to group allocation. The primary outcome for this analysis was the incidence of maternal placental vascular lesions. RESULTS: During the study period, 88 placentas were examined; 41 and 47 from the fixed and adjusted dose groups, respectively. Demographics, obstetrics and types of thrombophilias were similar between the groups. Maternal placental vascular lesions were observed in 23 (56.1%) and 21 (44.68%) placentas (p = 0.28) and foetal placental vascular lesions in 2 (4.88%) and 1 (2.13%) placentas (p = 0.59) in the fixed and adjusted groups, respectively. CONCLUSION: Adjusted dose of enoxaparin according to anti-factor Xa levels compared with a fixed dose did not affect placental vascular lesions in thrombophilic women.

Increased coagulation index as measured by Thromboelastography during ovarian stimulation for in vitro fertilization: Influence of the final oocyte maturation triggering agent.

OBJECTIVE: Thromboelastography (TEG) is a viscoelastic test of hemostasis which allows measurement of the processes of clot initiation, propagation, stabilization, and dissolution in real time. In this study we aimed to evaluate the alterations in coagulation as measured by TEG during In Vitro Fertilization (IVF) stimulation cycles and to investigate whether final oocyte maturation with recombinant hCG (rhCG) versus GnRH agonist results in a different coagulation state. STUDY DESIGN: This is a prospective observational study which included fifty-three normogonadotrophic women. All the patients received an antagonist IVF treatment protocol. Final oocyte maturation was triggered with either rhCG (n = 25) or GnRH agonist (n = 26). Two patients did not complete the study due to poor response. Venous blood was drawn in the early and late follicular phase and on the day of ovum pickup. The TEG parameters assessed were R (time to first clot formation), K (time until the clot reaches a fixed strength), alpha angle (the rate of clot formation), MA (reflects maximum strength of the platelet-fibrin clot), LY30 (percent of clot lysis at 30 min after MA is reached) and the CI (the overall coagulability). RESULTS: The overall coagulation index of the entire study population was significantly increased on the day of ovum pickup as compared to the early follicular phase. This increase in the coagulation index was also significant in a subanalysis of patients triggered with rhCG. Contrarily, there was no significant increase in the coagulation index in the subgroup of patients triggered with GnRH agonist. CONCLUSION: Our results demonstrate a procoagulable state in patients after ovulation induction. Final triggering with GnRH agonist rather than rhCG, might lower this hypercoagulability pattern.

Venous thromboembolism: the prevailing approach to diagnosis, prevention and treatment among Internal Medicine practitioners.

BACKGROUND: Venous thromboembolism (VTE) is the third most common cause of death and the leading cause of sudden death in hospitalized medical patients. Despite the existence of guidelines for prevention and treatment of this disorder, their implementation in everyday life is not always accomplished. METHODS: We performed a survey among directors of Internal Medicine departments in our country in order to evaluate their attitude and approach to this issue. A questionnaire with pertinent questions regarding prevention and treatment of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE) was sent to each one of the directors of Internal Medicine Departments around the country. RESULTS: Sixty-nine out of 97 (71%) of the Internal Medicine departments directors responded the questionnaire. We found that several of the current guidelines were followed in a reasonable way. On the other hand, heterogeneity of responses was also present and the performance of current guidelines was imperfectly followed, and showed to be deficient in several aspects. CONCLUSIONS: An effort should be done in order to reemphasize and put in effect current guidelines for the prevention and treatment of VTE among hospitalists and Internal Medicine practitioners.

Adjusting enoxaparin dosage according to anti-FXa levels and pregnancy outcome in thrombophilic women. A randomised controlled trial.

Women with thrombophilias and previous placenta-mediated pregnancy complications (PMPC) have an increased risk of both recurrent PMPC and venous thromboembolism (VTE) during subsequent pregnancies. We aimed to examine whether enoxaparin dose adjusted according to anti-factor Xa levels compared to a fixed dose would reduce the risk of PMPC in subsequent pregnancies. In a randomised trial, conducted at a single teaching hospital, pregnant women with thrombophilia and previous PMPC were enrolled in a 1:1 ratio to either a fixed dose of 40 mg daily enoxaparin or adjusted dose according to anti-factor Xa plasma levels. The primary outcome was a composite that included any of the following: pregnancy loss after enrollment, pre-eclampsia, birthweight <10th percentile, placental abruption, or VTE. Overall, 144 women were needed to detect a decrease of 20 % in the incidence of the composite outcome among the adjusted dose group. Between 2009 and 2015, 144 women consented; four in the fixed-dose group were excluded. Overall, 66 and 74 in the fixed- and adjusted-dose groups, respectively, were included. Demographic and obstetric characteristics were comparable. Composite outcome occurred in 12 (18.2 %) and 20 (27.0 %) women in the fixed- and adjusted-dose groups, respectively (p=0.24). Gestational age at delivery, preterm births, and birthweights were similar between the two groups. In conclusion, dose of enoxaparin adjusted according to anti-factor Xa levels compared to fixed dose, does not reduce the risk of PMPC recurrence in thrombophilic women.

Experiences in a family with the Upshaw-Schulman syndrome over a 44-year period.

A family with a novel c.717_del frameshift and a c.3655C > T missense mutation of a disintegrin and metalloproteinase with thrombospondin type I motif, member 13 protein (ADAMTS13) is described. Family members have been under observation for 44 years. Two double heterozygotes have severe early-onset Upshaw-Schulman syndrome and require prophylactic plasma infusions. Analysis reveals that 2 weekly plasma infusions are not sufficient in preventing laboratory evidence of a thrombotic thrombocytopenic purpura (TTP) attack. Both the double heterozygotes also have a heterozygous factor V Leiden G1291A mutation. One underwent splenectomy, which did not reduce the frequency of TTP episodes but resulted in a recurrent pulmonary embolism and has necessitated lifelong anticoagulant therapy. The other has mild chronic renal failure and has had episodes of atrial fibrillation and cerebral infarction. Of the 3 heterozygotes in the family, 1 has had episodes of mild thrombocytopenia.

Allogeneic stem cell transplantation for patients with chronic myeloid leukemia: risk stratified approach with a long-term follow-up.

The use of allogeneic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) was almost abandoned in recent years for very effective targeted therapy with tyrosine kinase inhibitors (TKIs). However, approximately one third of patients still need another treatment including SCT. 38 consecutive CML patients were treated (most in preimatinib era) with allogeneic SCT, using partial T cell depletion (TCD) and preemptive donor lymphocyte infusion (DLI), without post-transplant graft-versus-host disease (GvHD) prophylaxis. Conditioning included busulfan, cyclophosphamide, antithymocytic globulin, and fludarabine followed by donor stem cell transfusion. With a median follow up of 90.5 months (1-134), 32 patients are alive. 97% engrafted. 5-year leukemia free survival (LFS) and overall survival (OS) were 78.95% and 84.2%, respectively. All patients are in major molecular remission and 78% in complete molecular remission. Transplant-related mortality (TRM) was 13%. Twenty-four patients received DLI for residual disease. Acute GvHD, mostly Grades I-II, occurred in 18% of patients post-transplant and in 24% of patients receiving DLI. In conclusion, the risk-adapted approach using only partial TCD and preemptive escalated dose of DLI precluded the need for immunosuppressive medications and reduced the risk of significant GvHD without compromising engraftment and long-term disease control. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.

Imatinib plasma trough levels in chronic myeloid leukaemia: results of a multicentre study CSTI571AIL11TGLIVEC.

Imatinib has been accepted as frontline treatment for patients with chronic myeloid leukaemia (CML), and patients generally receive doses ranging from 400 to 800 mg/day. Previous studies have demonstrated that maintaining imatinib plasma levels (IMPLs) >1000 ng/mL leads to improved responses and long-term outcomes. However, IMPLs vary among patients because of factors such as drug-drug interactions, adherence, toxicity and differential levels of expression of cellular efflux/influx proteins. In this study, IMPLs were analysed in 191 patients with CML and were compared with achievement of molecular and cytogenetic responses (CyR). IMPLs were also correlated with renal and hepatic dysfunction. Additionally, self-reported adherence was monitored. The median and mean IMPLs were 994 ng/mL and 1070 ± 686 ng/mL, respectively, with 96 patients (50%) achieving plasma levels >1000 ng/mL. Self-reported patient compliance was 98%. Patients who achieved a complete CyR (CCyR) had significantly higher IMPLs (1078 ± 545 ng/mL) than those without CyR (827 ± 323 ng/mL, p = 0.045). When grouped together, patients who achieved a CCyR or partial CyR had significantly higher IMPLs than patients who achieved a minimal CyR or did not achieve a CyR (1066 ng/mL vs 814 ng/mL, p = 0.002). There was no significant difference observed in the IMPLs between patients who achieved molecular responses (n = 177) on treatment (major molecular response, 976 ± 385 ng/mL versus complete molecular response, 1138 ± 809 ng/mL, p = 0.387). Mean IMPLs were similar in patients with or without renal or hepatic impairment. Overall, this study confirmed previous reports that higher IMPLs correlate with clinical responses and demonstrated that imatinib exposure did not differ in patients with or without liver and/or renal dysfunction. The use of IMPL testing and patient diaries may be practical tools for the management of imatinib therapy in patients with CML.

Meta-analysis of unexpected findings in routine histopathology during total joint replacement.

BACKGROUND: Routine histopathological analysis of bone extracted during total joint replacement is controversial. OBJECTIVES: To evaluate the utility of routine histopathological analysis in total joint replacement. METHODS: We calculated the risk for discrepant diagnosis between the pre- and postoperative histopathological results by performing a meta-analysis of 11 studies (including our data). We also calculated the risk for significant discrepancies. RESULTS: The discrepant diagnoses analysis showed a random effect of 3% discrepancies (95% confidence interval 1.2-3.7%). Funnel plot indicates a publication bias; consequently, the conclusions from this analysis should be interpreted with caution. Regarding the significant discrepancy in diagnosis, we performed a meta-analysis of nine studies. Fixed-effects analysis of all the studies resulted in 0.16% significant discrepancies (95% CI 0.02-0.30%) with no heterogeneity (Q = 3.93, degrees of freedom = 9, P = 0.14, /2 = 49.2%), and appropriate fixed-effects models. CONCLUSIONS: We recommend no further routine histological examination, reserving this tool for cases with a controversial primary diagnosis and unexpected findings during the operation.

Air travel and the risk of thromboembolism.

Almost two billion people use commercial aircraft annually. Long-haul flights are taken by over 300 million people. A serious complication of long-distance travel (or prolonged time of flight) is thromboembolism. The real incidence of the problem is difficult to evaluate since there is no consensus about the diagnostic tests or limitation of time after landing connected to the VTE complication. A direct relation between VTE incidence and long-distance flights has been documented. The risk for DVT is 3-12% in a long-haul flight. The pathophysiologic changes that increase VTE risk at flight are stasis (sitting in crowded condition), hypoxia in the airplane cabin, and dehydration. Individual risk factors for air travel-related VTE include age over 40 years, gender (female), women who use oral contraceptives, varicose veins in lower limbs, obesity and genetic thrombophilia. Prevention measures include environmental protection such as keeping the pressure inside the airplane cabinet in hypobaric condition, avoiding dehydration and prolonged sitting. For individuals at increased risk, venous blood stasis can be reduced by wearing elastic stockings and prophylactic use of low-molecular-weight heparin.

Rituximab monotherapy for splenic marginal zone lymphoma.

In this retrospective study, rituximab was found to be effective therapy in 10 of 11 patients with splenic marginal zone lymphoma, inducing prompt reduction in splenomegaly, improvement in blood counts in 9 patients and clearance of a pleural effusion in 1 patient. Median response duration was 21 months (range 4 to 37 months). Two patients who relapsed at 21 and 23 months responded to retreatment. Rituximab should be considered in patients who are poor candidates for splenectomy.