Amihai Rottenstreich

The role of N-acetylcysteine in the treatment of thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is an acute, thrombotic microangiopathy with a high mortality rate if left untreated. Plasma exchange (PEX) is the current standard of care. However, a significant number of patients are refractory to this treatment. N-acetylcysteine (NAC) was recently suggested as a potential therapeutic adjunct for patients with TTP. This study reports a series of three patients with TTP successfully treated with NAC in addition to standard therapy. Detailed chart reviews on these patients were conducted. We discuss clinical features, laboratory findings and management of three patients who presented with microangiopathic hemolytic anemia and thrombocytopenia. Anti-ADAMTS13 antibodies and low levels of ADAMTS13 were detected and confirmed the diagnosis of acquired TTP. Based upon their severe presentation or lack of response to initial treatment with PEX, corticosteroids and other immunosuppressive agents, NAC was added. Under this combined treatment, all three patients hada significant clinical improvement of symptoms with concurrent normalization of platelet count and ADAMTS13 activity level. This report highlights the potential therapeutic utility of NAC in the treatment of TTP. Randomized controlled studies will be required to better characterize the risk-to-benefit ratio of NAC in the treatment of TTP.

Abdominal thrombotic complications following bariatric surgery.

BACKGROUND Thrombotic events involving the portal-splenic-mesenteric venous system (PSMVT) are rare but potentially lethal after bariatric surgery. OBJECTIVES To investigate the incidence, clinical presentation, management, and outcome of thrombotic events after bariatric surgery. SETTING Two university hospitals. METHODS A retrospective review of individuals who underwent bariatric surgery between January 2006 and December 2015. RESULTS Overall, 4386 patients underwent bariatric surgery (laparoscopic sleeve gastrectomy [LSG; n = 2886], laparoscopic Roux-en-Y gastric bypass [n = 762], laparoscopic adjustable gastric banding [n = 668], and biliopancreatic diversion [n = 70]). Mechanical (thigh-length pneumatic compression stockings) and pharmacologic thromboprophylaxis (40 mg enoxaparin daily, starting 12 hours after surgery until discharge) was provided for all patients. A minority of patients (n = 543, 12.4%) also received an extended course of enoxaparin for 1-4 weeks after discharge. We observed 16 cases of PSMVT, all after LSG, with an incidence of .55% (16/2886). Twelve additional patients experienced deep vein thrombosis and 6 had pulmonary embolism. Follow-up imaging indicated complete resolution in all cases, with no sequelae, recurrent thrombosis, or mortality. The overall thrombosis rate was significantly lower in patients who received an extended course of anticoagulation after LSG (P = .01) and after any type of bariatric surgery (P = .02). CONCLUSIONS PSMVT was found to occur uncommonly after LSG. Prompt diagnosis and anticoagulation therapy led to favorable outcomes in most cases. Significantly lower rates of thrombosis were found in patients who received an extended course of anticoagulation. We support its use for at least 1 week after discharge.

Sleeve gastrectomy and mesenteric venous thrombosis: report of 3 patients and review of the literature

haim Mesenteric venous thrombosis (MVT) is a rare but potentially lethal pathology. Although first described by Balfour and Stewart in 1869 [1], it was first presented as a distinct cause of mesenteric ischemia by Warren and Eberhand only in 1935 [2]. MVT accounts for 5%–15% of all mesenteric ischemic events [2,3]. In the past, MVT has been described after procedures involving manipulation of the portal venous system, such as splenectomy or liver transplantation [4,5]. However, since the beginning of the minimal invasive era, MVT has occurred in several cases after various laparoscopic procedures [6]. During the last decade, a few cases of MVT have been published to occur after laparoscopic bariatric operations, including laparoscopic sleeve gastrectomy (LSG) [7]. Nevertheless, MVT has been shown to be a major morbidity during the perioperative period of LSG with an incidence of 1% [8]. The aim of this article is to present 3 cases of MVT that have occurred after 900 LSG procedures in our center, discuss the pathophysiology and management of this complication and suggest preventive strategy.

Hypoglycemia During Oral Glucose Tolerance Test Among Post-Bariatric Surgery Pregnant Patients: Incidence and Perinatal Significance

BACKGROUND While hypoglycemia during an oral glucose tolerance test (OGTT) has been shown to occur in a considerable portion of nonpregnant post-bariatric surgery (BS) patients, its incidence among pregnant post-BS patients evaluated for gestational diabetes has only been sparsely studied. OBJECTIVES We investigated OGTT results and pregnancy outcomes in pregnant women who underwent 3 types of bariatric procedures before pregnancy. SETTING A university hospital. METHODS From medical records, data were collected on glucose measurements during a 100-g, 3-hour OGTT, as well as maternal and fetal outcomes. RESULTS Of 119 post-BS pregnant patients included in the study, 55 underwent laparoscopic sleeve gastrectomy, 34 laparoscopic adjustable gastric banding, and 30 laparoscopic Roux-en-Y gastric bypass surgery. Hypoglycemia (<55 mg/dL) was encountered in 59 (49.6%) patients during the OGTT. Among them, the nadir plasma glucose levels occurred 2 hours after glucose ingestion in 25 (42.4%) and after 3 hours in 34 (57.6%), with a median value of 47 (44-52) mg/dL. The risk of hypoglycemia was higher among women with prior laparoscopic Roux-en-Y gastric bypass surgery (83.3%) than among those with prior laparoscopic sleeve gastrectomy (54.5%; P = .009) or laparoscopic adjustable gastric banding (11.8%; P<.0001). Time from surgery to conception was significantly shorter among women with evidence of hypoglycemia during OGTT (median 711 versus 1246 days, P = .002). Compared with patients without evidence of hypoglycemia, patients who experienced hypoglycemia had lower rates of gestational diabetes (P = .03) but higher proportions of low birth weight (P = .01) and small for gestational age infants (P = .03). CONCLUSIONS Because hypoglycemia is common during OGTT among post-BS parturients, other diagnostic methods should be considered in this setting. The association found between hypoglycemia and poor fetal growth warrants investigation as to whether interventions to prevent hypoglycemia will improve fetal outcome.

Factors related to the development of acquired von Willebrand syndrome in patients with essential thrombocythemia and polycythemia vera

OBJECTIVE We characterized acquired von Willebrand syndrome (AVWS) among essential thrombocythemia (ET) and polycythemia vera (PV) patients. METHODS A review of patients with ET or PV evaluated for AVWS. RESULTS Of 116 patients with ET, 64 (55%) developed AVWS; of 57 with PV, 28 (49%) developed AVWS. Median platelet counts of ET and PV patients who developed AVWS were 920×109/L and 679×109/L, respectively (P=0.01). Of patients who developed AVWS, 69.5% had platelet counts below 1000×109/L. Bleeding was more common in patients with AVWS, among both ET and PV patients (P<0.001). VWF:RCo levels and VWF:RCo/VWF:Ag ratio were lower among JAK2 V617F positive- vs. JAK2 V617F negative- ET patients (P=0.02 and P=0.002, respectively); whereas VWF:Ag levels were comparable (P=0.96). ET patients harboring the JAK2 V617F mutation were more likely to develop AVWS than were calreticulin-positive patients (70.3% vs. 45.7%, P=0.02), despite lower platelet counts (median 773 vs. 920×109/L, P=0.05). In multivariable analysis, younger age (P=0.002), platelet count (P<0.001), hemoglobin level (P=0.01) and JAK2 V617F mutation (P=0.01) independently predicted the development of AVWS among ET patients; whereas only platelet count predicted its development among PV patients (P<0.001). CONCLUSION Among ET and PV patients, AVWS was common and associated with higher bleeding rates and higher platelet count; nonetheless, most AVWS patients had platelet counts under 1000×109/L. Thus, AVWS screening should be included in routine assessment of ET and PV patients. Among ET patients, JAK2 V617F was a main driver for the development of AVWS.

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.

The effect of bariatric surgery on direct-acting oral anticoagulant drug levels

OBJECTIVE To determine direct-acting oral anticoagulant (DOAC) blood levels in post-bariatric surgery (BS) patients treated with long-term anticoagulation therapy. METHODS We identified from medical records patients who underwent BS during 2005-2016 and who were treated with DOACs. We offered testing DOAC blood levels to these patients and to age, sex, body mass index, and serum creatinine-matched individuals treated by DOACs who did not undergo BS. RESULTS Overall, 36 individuals were enrolled, 18 post-BS patients and 18 control subjects. Of the post-BS patients, 12 underwent laparoscopic sleeve gastrectomy, 4 laparoscopic adjustable gastric banding and 2 laparoscopic Roux-en-Y gastric bypass surgery. Median time lapsed from surgery until study inclusion was 4.9years. Five post-BS patients had peak drug levels below expected levels compared to none of the control subjects (P=0.05). For patients who used apixaban (n=9) and dabigatran (n=2), peak drug levels were within the expected range. In contrast, for the 7 patients who used rivaroxaban, levels were below the expected range in 5, including all four who underwent sleeve gastrectomy and one following adjustable gastric banding. Peak rivaroxaban levels were significantly lower in the post-BS than the control group (P=0.02). CONCLUSION This preliminary study suggests that all DOACs, particularly rivaroxaban, be cautiously used following BS, if used at all. Given that vitamin-K antagonists can be easily monitored, they may be a better choice, until more data on DOAC use in this patient population are available.

A Rare Case of Benign Pneumatosis Intestinalis with Portal Venous Gas and Pneumoperitoneum Induced by Acarbose

Alpha glucosidase inhibitors have been shown to be associated with pneumatosis intestinalis (PI) in recent reports. We herein report the case of a 73-year old man who received treatment with an alpha glucosidase inhibitor (acarbose) and presented with acute abdomen. A computed tomography scan demonstrated PI in addition to intrahepatic portal air and pneumoperitoneum. During exploratory laparotomy, we found no evidence of hollow organ perforation or bowel necrosis. The patient recovered after conservative treatment with cessation of the alpha glucosidase inhibitor. This is the first report to describe the combination of PI with portal venous gas and pneumoperitoneum caused by an alpha-glucosidase inhibitor.

Assessment of procoagulant potential in patients with reactive thrombocytosis and its association with platelet count

We aimed to determine hemostatic changes and characterize the procoagulant potential among patients with reactive thrombocytosis (RT).

Iatrogenic Cushing Syndrome due to Intranasal Dexamethasone

With increasing use of intranasal steroids for a wide range of pediatric upper airway disorders, the potential for iatrogenic CS with these agents should be considered. We describe a case of a 7-month-old infant who developed CS secondary to intranasal use of dexa-methasone. Written informed consent was obtained from the parents for publication of this case report.