Yosef Kalish

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.

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.

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).

Assessment of the procoagulant potential after laparoscopic sleeve gastrectomy: a potential role for extended thromboprophylaxis

BACKGROUND Bariatric surgery is associated with increased thromboembolic risk, which may extend well beyond hospital stay. The hemostatic mechanisms implicated in this risk are not well established. OBJECTIVES We aimed to determine the dynamics of hemostatic changes and procoagulant potential among patients undergoing laparoscopic sleeve gastrectomy, during both the early and late postoperative periods. SETTING A university hospital. METHODS Patients who underwent laparoscopic sleeve gastrectomy were recruited consecutively to this study. Blood samples were taken preoperatively, before discharge (postoperative day [POD] 3), and at the first follow-up visit (POD10). All samples were tested for complete blood count, C-reactive protein, von Willebrand factor, factor VIII, fibrinogen, and thrombin generation. RESULTS The median preoperative body mass index of the 26 participants was 41.3 (38.7-43.3) kg/m2. Compared with preoperative evaluation, fibrinogen, von Willebrand factor antigen and activity, and factor VIII levels were significantly higher at POD3 and POD10 (P<.0001 for all comparisons). Peak thrombin levels and endogenous thrombin potential (ETP) were higher at POD3 (P = .005 for both comparisons) and POD10 (P = .0009 and<.0001) compared with baseline. ETP and peak thrombin, as well as fibrinogen, von Willebrand factor, and factor VIII levels, were comparable between POD3 and POD10. Multivariate analysis showed that the only predictor of postoperative ETP was the preoperative ETP level (β = .55, P = .007). CONCLUSIONS As determined by thrombin generation, laparoscopic sleeve gastrectomy was associated with hypercoagulability, which persisted during POD10. This finding suggests a possible benefit of extended thromboprophylaxis. Nevertheless, our results should be interpreted with caution due to the lack of a control group.

Retrievable inferior vena cava filter utilization in obstetric patients

Abstract Objectives: The objective of this study is to evaluate patterns of use and outcomes of retrievable inferior vena cava filters (rIVCF) in obstetric patients. Methods: A single center review of consecutive patients who underwent rIVCF placement during pregnancy/postpartum in 2005–2016. A pooled analysis of the relevant cases in the English literature was conducted. Results: The current cohort comprised 24 women, median age 27 [interquartile range 24–30] years. Among 10 filters placed during pregnancy, the most common indication (n = 4) was the need to withhold anticoagulation therapy before delivery, in the presence of acute thrombosis. In the postpartum period, most filters (64%, 9/14) were an adjunct to catheter-directed thrombolytic therapy. Inferior vena cava filters (IVCF)-related complications occurred in seven (29.2%). Retrieval was attempted in 21 patients (87.5%), and was technically successful in 19 (90.5%), for an overall removal rate of 79.1%. Pooled analysis of the literature (n = 98) showed comparable rates for filter removal and complications (81.6%, p = .78 and 24.2%, p = .60, respectively). Suprarenal placement (p = .12) and elective cesarean section (p = .19) did not reduce overall complication and retrieval rates. The estimated radiation dose among pregnant patients who underwent rIVCF placement without adjunct catheter directed thrombolysis (CDT) (mean 695 Gy cm2) was significantly lower than the radiation dose used in postpartum patients (1863 Gy cm2) or in pregnant patients in whom adjunct CDT was utilized (4059 Gy cm2) (p = .001 for both comparisons). Conclusions: Frequent rIVCF-related complications, radiation exposure, and removal failure call for their cautious utilization in obstetric patients. The role of suprarenal placement and elective cesarean section to improve outcomes has yet to be established.

Acquired thrombotic thrombocytopenic purpura in pregnancy: The role of placental and breast-milk mediated transfer of ADAMTS13-autoantibodies

To the editor: Acquired thrombotic thrombocytopenic purpura (TTP) is an acute, life threatening thrombotic microangiopathy resulting from autoantibodymediated inhibition of ADAMTS13 (ADisintegrin AndMetalloproteinase with a Thrombospondin type 1 motif, member 13), the key enzyme involved in the cleavage of ultra-large von Willebrand factor multimers [1]. Approximately 5–10% of TTP cases are encountered in the setting of pregnancy, with associated adverse maternal and fetal outcomes [1]. Herein we describe a case of acquired TTP in a pregnant patient and depict the role of anti-ADAMTS13 antibodies in the fetus.

Factors associated with thromboembolic events following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

We investigated the risk factors, incidence, and role of thromboprophylaxis in the development of thrombosis following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).