Pharmacomechanical catheter thrombolysis for pregnancy-related proximal deep venous thrombosis: prevention of post-thrombotic syndrome.

OBJECTIVE: The efficacy of pharmacomechanical catheter-directed thrombolysis (PCDT) in preventing post thrombotic syndrome (PTS) for pregnancy related deep vein thrombosis (DVT) is unknown. STUDY DESIGN: An observational cross section study of women with pregnancy related proximal (femoral/iliofemoral) DVT who underwent PCDT followed by anticoagulation (study group), and women who were treated with anticoagulation alone (control group). Women were evaluated for PTS using the Villalta scale (primary outcome) and VEINES-QOL/Sym questionnaires. RESULTS: Eleven women with iliofemoral DVT underwent PCDT, two during their first trimester and nine postpartum; 18 women were treated with anticoagulation only. There were no significant differences in age, number of previous pregnancies, and duration of anticoagulation or thrombophilia between the groups. The time between DVT diagnosis and study inclusion was longer in the study group [median 50.5 (range 16-120) months] compared to the control group [median 27 (range 11-64) months], p = .4. None of the women in the PCDT group developed PTS, compared to six (33.3%, p = .03) in the control group, four of whom developed severe PTS. One patient in each group developed recurrent DVT, and one patient in the study group developed a calf hematoma. A reduced frequency of lower extremity symptoms was observed in the PCDT group (VEINES-Sym questionnaire), but no differences in quality of life (VEINES-QOL questionnaire) were reported. CONCLUSION: This study suggests that PCDT may reduce the incidence of PTS in women with pregnancy related proximal DVT.Bullet pointsDVT involving the iliofemoral veins and development of post thrombotic syndrome is frequent among pregnant or postpartum womenStudies of pharmacomechanical catheter-directed thrombolysis (PCDT) for deep vein thrombosis did not include pregnant or postpartum womenIn our observational cross section study women who underwent PCDT (mainly in the postpartum period) had reduced frequency of post-thrombotic syndrome compared to women who received anticoagulation onlyLarger studies are required to confirm the use of PCDT for prevention of PTS in this population.

Internal medicine patients admitted without COVID-19 during the outbreak.

BACKGROUND: The first case of COVID-19 in Israel was reported on February 21, 2020. Shaare Zedek (SZ), a 1000-bed tertiary care medical centre in Jerusalem, Israel, cared for a significant number of these patients. While attention focused on COVID-19 patients, uninfected patients were admitted to decreasing numbers of available internal medicine (IM) beds as IM departments were converted to COVID-19 isolation wards. As a result of the increase in COVID-19 patients, closure of IM wards, re-assignment of staff and dynamic changes in available community placement options, we investigated the impact of the outbreak on IM patient not admitted for COVID-19. METHODS: We reviewed IM admissions during March 15-April 30, 2020 for patients without COVID-19. Characteristics assessed included number of admissions, age, length of stay, mortality rate, number of discharges, number discharged home and functional status of the patients. Data were compared with the previous 3 years (2017-2019) during the same time period. RESULTS: During March 15-April 30, 2020 there were 409 patients admitted to IM compared with a mean of 557 over the previous 3 years. Fewer patients were admitted to the ED and the IM wards during the outbreak. There was no significant difference between the two groups with regards to gender, in-hospital mortality rate, number discharged, number discharged home and patient functional level. Patients admitted during the outbreak to IM were younger (74.85 vs 76.86 years) and had a mean shorter hospital length of stay (5.12 vs 7.63 days) compared with the previous 3 years. CONCLUSION: While the characteristics of patients admitted to IM during the outbreak were similar, hospital length of stay was significantly shorter. Internal management processes, as well as patient preferences may have contributed to this observation. An infectious disease outbreak may have a significant effect on uninfected admitted patients.

Risk factors associated with neonatal thrombocytopenia in pregnant women with immune thrombocytopenic purpura.

Objectives: To characterize the risk factors associated with neonatal thrombocytopenia among pregnant women with immune thrombocytopenic purpura (ITP).Methods: We reviewed the records of ITP patients who delivered during 2006-2016 at our medical center.Results: Of 253 pregnancies, median maternal age at diagnosis was 29 [25-33] years, 222 (87.7%) had previously-diagnosed ITP and 31 (12.3%) were diagnosed with new-onset ITP during pregnancy. Baseline characteristics were comparable between the groups except for a higher proportion of nulliparity among those with new-onset disease (p = .002). Maternal nadir platelet count was significantly lower among those with new-onset compared to previously diagnosed ITP (median 62 × 109/L versus 81 × 109/L, p = .005). Neonatal thrombocytopenia (<150 × 109/L) was encountered in 24 (9.5%) pregnancies and required treatment in 12 (50%) of them. Neonatal platelet count was directly correlated with maternal platelet count at delivery (r = 0.23, p = .01), with significantly lower maternal platelet count among those whose newborns experienced thrombocytopenia (p < .001). Neonatal thrombocytopenia followed a higher proportion of pregnancies of women with new-onset than previously diagnosed ITP (22.6 versus 7.7%, p = .02). In multivariate analysis, the presence of new-onset ITP (odds ratio [95% CI]: 4.88 (1.68, 14.16), p = .004) was the only independent predictor of the development of neonatal thrombocytopenia.Conclusion: Neonatal thrombocytopenia presented following almost one-tenth of pregnancies with ITP. New pregnancy-onset disease was the only prognostic marker for neonatal thrombocytopenia. This finding could contribute to risk stratification and individualized patient management.

Factors associated with pregnancy outcomes in women with a history of cerebral sinus venous thrombosis.

To collect and summarize pregnancy outcomes among women with a history of cerebral sinus vein thrombosis (CSVT). A retrospective multicenter case-control study. The study group comprised all women diagnosed with CSVT during 2004-2018 at four university hospitals, and with follow-up data of pregnancy. A control group of women with a singleton pregnancy was established by matching, four-to-one, according to maternal age. The data of 74 pregnancies of 65 women with CSVT were analyzed. The median time-to-pregnancy interval from the CSVT was 4.2 [2.7-6.8] years. Anticoagulation therapy in the form of enoxaparin was administered in 68 (91.9%) pregnancies. Adjunctive low-dose aspirin was used throughout 12 (16.2%) pregnancies. Overall, 54 (73.0%) of the pregnancies ended in live births and 20 (27.0%) in miscarriage. The use of anticoagulation therapy during pregnancy was positively associated with live birth outcome (P < 0.001). Late adverse outcomes were encountered in 19 (25.7%) pregnancies, including the delivery of a small for gestational age infant (n = 12), gestational hypertensive disorders (n = 6) and placental abruption (n = 3). The use of adjunctive aspirin was associated with a lower rate of late adverse pregnancy outcomes (P = 0.03). No recurrent CSVT, thrombosis at other sites, and major bleeding episodes were observed during pregnancy. Live-birth rate was higher (P = 0.007) and the rate of late adverse outcome was lower (P = 0.01) for the control (n = 296) than the study group. Among pregnant women with a prior CSVT, no recurrent thrombosis events were observed during gestation. The use of prophylactic anticoagulation was associated with live birth. The use of adjunctive aspirin should be further studied in this setting, as its utilization correlated with a lower rate of late pregnancy complications.

Direct-acting oral anticoagulant drug level monitoring in clinical patient management.

The role of drug-level monitoring among patients using direct-acting oral anticoagulant (DOAC) is unclear. We aimed to investigate its 'real-life' utilization and effect on clinical management. A review of records of patients who underwent DOAC level testing during 2013-2017. Overall, 212 patients (median age 77 years) underwent 292 DOAC measurements [apixaban (n = 147), rivaroxaban (n = 102), dabigatran (n = 43)]. Monitoring volume increased by 460% during study period. DOAC level testing was performed during routine follow-up in 51 (17.5%) cases, whereas the remaining 241 (82.5%) measurements were performed due to selected clinical circumstances, most commonly: bleeding (n = 60), perioperative status (n = 45), breakthrough thrombosis (n = 37) and renal failure (n = 35). Drug levels were within the expected range in 210 (71.9%), above the expected range in 62 (21.2%) and lower than expected range in 20 (6.8%). In multivariate analysis, older age (P = 0.005), lower glomerular filtration rate (P = 0.001) and lower body mass index (P = 0.006) were associated with DOAC levels above the expected range. Clinical decisions were affected by DOAC monitoring following most (140/241, 58.1%) measurements for which we identified an indication for testing; yet only rarely when monitoring was performed during routine follow-up (7.8%, 4/51) (P < 0.0001). While no benefit of routine DOAC monitoring was observed, drug level measurement has an important role in the management of patients in selected circumstances. Age, body weight and creatinine clearance were found to be significant predictors of drug levels. Future studies are warranted to establish associations between drug levels and outcomes, and better delineate the role of DOAC monitoring.

Thromboembolic Events Following Splenectomy: Risk Factors, Prevention, Management and Outcomes.

BACKGROUND: Thromboembolic events following splenectomy are not uncommon. However, the role of thromboprophylaxis and risk factors for thrombosis, as well as the clinical course and outcomes, are not well characterized. METHODS: A retrospective review of individuals who underwent splenectomy between January 2006 and December 2015 in two university hospitals. RESULTS: Overall, 297 patients underwent splenectomy [open splenectomy (n = 199), laparoscopic splenectomy (n = 98)]. Mechanical (thigh-length pneumatic compression stockings) and pharmacologic thromboprophylaxis (40 mg enoxaparin daily, starting 12 h after surgery until discharge) was provided for all patients. One hundred and sixteen patients (39%) also received an extended thromboprophylaxis course of enoxaparin for 2-4 weeks after discharge. Twenty-three patients (7.7%) experienced thrombotic complications following splenectomy, including 16 cases (5.4%) of portal-splenic mesenteric venous thrombosis (PSMVT), 5 (1.7%) pulmonary embolism and 2 (0.7%) deep vein thrombosis. Longer operative time (mean operative time of 405 vs. 273 min, P = 0.03) was independently associated with PSMVT. Post-splenectomy thrombocytosis was not associated with thrombosis (P = 0.41). The overall thrombosis rate was significantly lower in patients who received an extended thromboprophylaxis course following splenectomy (3.4 vs. 10.5%, P = 0.02). Complete resolution of thrombosis was observed in most cases (n = 20, 87.0%), with no recurrent thrombosis during a mean follow-up of 38 ± 25 months. CONCLUSIONS: Thromboembolic complications, mainly PSMVT, are common following splenectomy. Longer operative time was associated with thrombosis. Significantly lower rates of thrombosis were found in patients who received an extended thromboprophylaxis course.

Active malignancy in patients with renal vein thrombosis: influence upon clinical course and survival.

BACKGROUND: Renal vein thrombosis (RVT) is a rare event with myriad clinical manifestations. Published experience regarding the clinical course and management of RVT in patients beyond the neonatal period is limited to case reports and small case series. METHODS: A multicenter retrospective review of consecutive admitted patients with diagnosed RVT between January 2000 and May 2015 at three different university hospitals. RESULTS: Thirty-nine patients (53.8 % men and 46.2 % women) were included. Median age was 58 years. Malignancy (n = 19, 48.7 %), nephrotic syndrome (n = 8, 20.5 %) and infection (n = 5, 12.8 %), were the most common underlying conditions. Compared to non-cancer patients, patients with active cancer tended to be significantly older (mean age 63 ± 18 vs. 37 ± 22 years, P = 0.001) and presented with non-acute symptoms (P = 0.01) and unrevealing physical findings (P = 0.02). Thrombosis extension beyond the renal vein occurred in 69.2 % of cases and was more common in cancer patients (P = 0.001). Anticoagulation therapy was administered in 71.8 % of patients leading to resolution of thrombus in most cases (30/32 patients, 94 %) during follow-up evaluation. There were six recurrent thrombotic events during a mean follow-up of 35 ± 43 months. Nine patients (28 %) died during follow-up, all of them with malignancy. CONCLUSION: Active cancer is the most common cause of RVT and should be excluded when RVT is diagnosed. Clinical course of RVT in cancer patients is more indolent and diagnosis requires high index of suspicion. Survival rates are governed by the presence of malignancy.

Pregnancy and non-pregnancy related ovarian vein thrombosis: Clinical course and outcome.

OBJECTIVE: To collect and summarize demographic, clinical, laboratory and radiologic characteristics, as well as management and follow-up data, of patients diagnosed with ovarian vein thrombosis. METHODS: A multicenter retrospective review of all patients diagnosed with ovarian vein thrombosis between January 2000 and May 2015 at three university hospitals. RESULTS: Data of 74 women were analyzed. Mean age was 31±9years. Sixty (81.1%) cases were pregnancy-related. The presence of at least one underlying risk factor (most commonly active infection or surgery) was more common among pregnancy than non-pregnancy related cases (61.7% vs. 14.3%, P=0.002). Anticoagulation therapy was administered in 98.6% of patients and adjunctive antibiotic therapy in 39 (52.7%). At a median follow-up of 40±38months, only one recurrent thrombotic event was observed, and no events of death. Median duration of anticoagulation treatment tended to be longer among patients with non-pregnancy related OVT (6months [3-14] vs. 3months [3-6], P=0.1). Thrombophilic evaluation detected any thrombophilic risk factor in 12 (20%) and 6 (42.9%) women with pregnancy and non-pregnancy related ovarian vein thrombosis, respectively (P=0.09). CONCLUSION: Pregnancy-related ovarian vein thrombosis is characterized by a provoked nature and a high rate of resolution after short term treatment. Treatment of three months duration of anticoagulation following this condition appeared in this study to be safe, with no recurrences encountered during a median follow up of 40months. Thrombophilia seems to have an important role in ovarian vein thrombosis and should be evaluated in non-pregnancy related cases.

Valproic acid-induced eosinophilic pleural effusion: a case report and review of the literature.

We present a case of eosinophilic pleural effusion due to valproic acid (VPA), a rare adverse event that has been reported previously. A 30-year-old male patient presented with respiratory symptoms and right-sided pleuritic pain, within days of initiation of VPA treatment for a generalized seizure. Chest radiography revealed a moderate-sized right-sided pleural effusion, which was an exudate with a pH of 7.54 and 48% eosinophils. Symptoms resolved soon after discontinuation of the drug, as did the effusion in a repeat radiograph 3 weeks later. The likelihood that VPA was the cause of the effusion is examined.

Plasma exchange as treatment for Lawsone (henna) intoxication.

Lawsone (2-hydroxy-1,4-naphthoquinone) is the active ingredient of Lawsonia alba, whose crushed leaves are known as henna, used as a hair and skin dye in many parts of the world. Accidental or deliberate ingestion of Lawsone has a high mortality rate (up to 31%) owing to rhabdomyolysis and renal failure. The authors report the first successful use of plasmapheresis as an adjunct to the treatment of these symptoms in a 69-year-old man who suffered severe symptoms of Lawsone poisoning due to inadvertent ingestion. Although most cases reported in the literature have been treated using supportive techniques, including hemodialysis, the high mortality despite these measures suggests that prompt plasma exchange may be a lifesaving technique for this syndrome.

Bleeding, obstruction, and perforation in a series of patients with aggressive gastric lymphoma treated with primary chemotherapy.

BACKGROUND: The management of patients with gastric lymphoma has evolved, with a shift toward nonsurgical treatment. The rates of surgical complications in patients receiving chemotherapy have been insufficiently studied. The objective of this study was to assess the frequency of bleeding, perforation, and gastric outlet obstruction in patients who received chemotherapy as primary treatment for gastric diffuse large B cell lymphoma (DLBCL). METHODS: We reviewed files of all patients with gastric DLBCL who were diagnosed and treated primarily with chemotherapy in our hospital between 1990 and 2005. RESULTS: Eighteen (25%) of 73 patients experienced surgical complications, of whom 6 (8%) underwent surgery. Eight patients (11%), six with active lymphoma, experienced gastric bleeding; one required gastrectomy. Eight patients (11%) developed gastric outlet obstruction, of whom three were treated conservatively, three required surgery, one stopped treatment, and one received further chemotherapy. Six of the eight patients had no evidence of active lymphoma at the time of obstruction. Two additional patients underwent gastrectomy due to resistant or relapsed disease. Gastric perforation was not observed. Median survival was 90 months for the entire series, 94 months for patients with gastric outlet obstruction, and 11.5 months for patients with gastric bleeding. CONCLUSIONS: Given the rate of surgical complications, especially gastric bleeding and gastric outlet obstruction, there is still an important role for the surgical consultant in the treatment of patients with gastric DLBCL receiving chemotherapy. Gastric perforation, although frequently cited as a complication, is in fact rarely observed.

Retreatment with rituximab alone induces sustained remission in a patient with follicular lymphoma with multiple extranodal sites of involvement, relapsing soon after primary treatment with fludarabine-rituximab.

Two recent studies have shown that retreatment of patients with relapsed indolent NHL with rituximab (RI) can be as effective as primary treatment, provided the lymphoma was initially responsive to primary RI therapy. From the available data, it remains unknown as to whether this approach is also effective for extranodal relapse. Here, we describe a 47-year-old male with stage 4B follicular lymphoma (FL), initially also involving skin, who achieved complete remission (CR) after a combination of fludarabine, cyclophosphamide and RI that lasted only 5 months. He soon relapsed with systemic disease and a number of extranodal sites including liver, lungs and bone marrow. After retreatment with RI alone (four cycles, 375 mg/m(2)), the patient achieved a second CR. Another four infusions of RI were given 6 months later as maintenance therapy. The duration of CR is already 18 months longer than the first CR. This case illustrates the fact that even in relapsed advanced FL, with multiple sites of extranodal disease, RI given as a single agent may be extremely effective in achieving an additional meaningful complete response.

Primary ALK positive anaplastic large cell lymphoma of the pancreas.

Here we present an unusual case of anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALCL), appearing as a primary tumor of the pancreas which invaded into the adjacent duodenal wall, causing upper gastrointestinal bleeding. After complete resection of the tumor (Whipple's operation), the patient received 4 cycles of CHOP chemotherapy. Currently, 2 years after diagnosis the patient still remains lymphoma free. Primary ALCL of the pancreas is very rare and has only been reported on one previous occasion. Nevertheless, lymphoma should be considered in the differential diagnosis of pancreatic tumors and an attempt to obtain tissue diagnosis is always necessary before continuing with radical surgery, especially in young patients.

Acute myocardial infarction as the presenting symptom of acute myeloblastic leukemia with extreme hyperleukocytosis.

This case report deals with an unusual leukostatic complication in a 56-year-old woman with acute myeloblastic leukemia (AML) and extreme hyperleukocytosis (316 x 10(9)/L) who presented with acute myocardial infarction (MI). After leukopheresis the patient achieved hemodynamic stabilization and rapid neurologic recovery of encephalopathy that had also developed after the infarction. Considering the central role of WBC in the remodeling of post MI myocardial tissue, it was obvious that administration of chemotherapy with its subsequent inevitable pancytopenia could impose an increased risk for further cardiac complications including myocardial rupture. Nevertheless, cytarabine-based induction chemotherapy was initiated 3 days after admission, and she achieved prolonged complete remission. Coronary angiography disclosed segmental atherosclerosis, but the only significant obstruction was in the right coronary artery. The patient died with relapsed leukemia 7 years later without recurrence of any cardiac symptoms or signs. Autopsy disclosed segmental coronary atherosclerosis involving the LAD (60% obstruction), suggesting that atherosclerosis was a predisposing risk factor. Additional compromise to blood perfusion due to leukostasis had led to this unusual complication of AML involving a major vessel. This is the first documented case of leukostasis causing coronary artery occlusion as well as the first report of successful induction chemotherapy for AML during a myocardial infarction.

Large-cell transformation of chronic lymphocytic leukemia and follicular lymphoma during or soon after treatment with fludarabine-rituximab-containing regimens: natural history- or therapy-related complication?

Novel therapeutic regimens containing purine analogs and monoclonal antibodies have led to significant improvement in the course of indolent lymphoproliferative diseases (LPD). Complete clinical and even molecular remissions have been achieved in an increasing proportion of patients. In parallel to their tumor cytotoxic effect, these agents are inevitably associated with prolonged immunosuppression inherent to their mechanism of antilymphocytic activity. Until now, attention has been paid mainly to opportunistic infection occurring as a result of the above drug-induced immunosuppression and less to other possible complications, such as malignancy or tumor progression in the immunocompromised host. Here we briefly report nine patients with previously treated indolent LPD in whom the onset of large-cell transformation occurred during or shortly after the initiation of regimens containing these agents before transformation occurred. One patient had received rituximab alone, three fludarabine-containing regimens and five received sequential regimens containing both agents. This

Agranulocytosis associated with initiation of famotidine therapy.

OBJECTIVE: To report a case of agranulocytosis associated with initiation of famotidine. CASE SUMMARY: An 87-year-old white man was admitted to the internal medicine department of an acute care hospital because of fever and agranulocytosis (granulocyte count 0). Eight days prior to admission, famotidine therapy had been initiated. Famotidine was discontinued and granulocyte-macrophage colony stimulating factor was administered, with concomitant recovery of the granulocyte count and subsequent development of a leukemoid reaction. DISCUSSION: According to the Naranjo probability scale, famotidine was the probable cause of agranulocytosis. This is a rare adverse effect of this medication; only a few other cases have been reported. CONCLUSIONS: Although agranulocytosis is a rare adverse effect of famotidine, the pharmacist and physician should be aware of this potentially fatal event. If any patient treated with famotidine develops fever, the clinician should consider, among other things, performing a white blood cell count.

Effects of the superoxide dismutase-mimetic compound tempol on endothelial dysfunction in streptozotocin-induced diabetic rats.

Evidence exists to support the beneficial effects of superoxide dismutase on endothelial dysfunction induced by hyperglycemia in vitro. In vivo, however, studies of the effects of native superoxide dismutase preparations on the vascular complications accompanying diabetes are limited, and their therapeutic application potential has so far been disappointing. The objective of this study was to evaluate, for the first time in vivo, the effects of long-term administration of tempol, a stable superoxide dismutase-mimic compound, on diabetes-induced endothelial dysfunction in rats. Diabetes was induced by streptozotocin and rats were monitored for 8 weeks with or without treatment with tempol (100 mg/kg, s.c., b.i.d). Diabetic rats showed increased vascular levels of superoxide, which was accompanied by increased levels of the oxidative stress markers malondialdehyde and 8-epi-prostaglandin F(2alpha). In addition, the vasorelaxant as well as the cGMP-producing effects of acetylcholine and glyceryl trinitrate were reduced in diabetic rats. Treatment with tempol abolished not only the differences in the vascular content of superoxide, malondialdehyde and 8-epi-prostaglandin F(2alpha), but also the differences in the relaxation and cGMP responses of aortic rings to both acetylcholine and glyceryl trinitrate between control and diabetic rats. These results support the involvement of reactive oxygen species in mediation of hyperglycemia-induced endothelial dysfunction in vivo, and provide the rationale for potential utilization of stable superoxide dismutase-mimic nitroxides for the prevention of the vascular complications accompanying diabetes.