Nabin Khanal

Management and Outcome of Heparin-Induced Thrombocytopenia in Pregnancy: A Systematic Review.

OBJECTIVEnSafety and efficacy of therapeutic agents used for heparin-induced thrombocytopenia are not established in pregnancy.nnnMETHODSnMEDLINE database was searched in November 2014 to identify all patients who received therapy for HIT during pregnancy.nnnRESULTSnA total of 12 patients with the median age of 28 years (range 21-39) were diagnosed with HIT at the median gestational age of 20 weeks (range 5-34). Clinical probability (4T) score for HIT was high (50%) or intermediate (50%) and associated with thrombosis in 50%. Patients were initially managed with lepirudin (33%), argatroban (25%), danaparoid (25%) or fondaparinux (17%) and ultimately bridged to vitamin K antagonist or maintained on lepirudin. All patients had resolution of HIT. Complications included therapeutic abortion prior to valve replacement for valve thrombosis (8%), preterm delivery (18%) and preeclampsia (8%). Except for one instance of hypoplastic lung related to preterm delivery, none of the other newborns had any complications during delivery.nnnCONCLUSIONnConfirmed cases of HIT in pregnant patients appear to be rare. Within the limits of retrospective analysis, the use of argatroban, danaparoid, fondaparinux and lepirudin may be effective in preventing the thrombotic complications of HIT in pregnancy. The effect of HIT or its therapy on obstetrical complications cannot be determined based on this study since many of the obstetrical complications are common in otherwise healthy pregnancies. Although this study did not identify any fetal teratogenicity except hypoplastic lung related to preterm delivery, small number of cases treated with various therapies precludes any definite conclusion.

Systemic therapy in stage IV pancreatic cancer: A population-based analysis using the National Cancer Data Base

Background: Pancreatic cancer accounts for approximately 7% of all cancer deaths. More than half of all pancreatic cancers are stage IV at diagnosis, where systemic chemotherapy is used with the goal of life prolongation as well as palliation. The patient characteristics and health system factors that drive the use of systemic therapy are unknown. Method: This is a retrospective study of stage IV pancreatic cancer patients (n = 140,210) diagnosed between 2000 and 2011 in the NCDB. NCDB contains approximately 70% of new cancer diagnosis from more than 1500 accredited cancer programs in the United States and Puerto Rico. Chi-squared test was used to determine any differences in characteristics of patients who did or did not receive systemic therapy. Results: Our study demonstrated that only 49.1% of stage IV pancreatic cancer patients received systemic therapy. The use of systemic therapy is significantly lower in female, African American/Hispanic, patients older than 40 years, those without insurance or with Medicare and Medicaid, higher Charlson Comorbidity Score, poor economic and educational status and in nonacademic centers. Conclusions: This is the largest study to evaluate the determinants of systemic therapy use in stage IV pancreatic cancer. The use of systemic therapy was significantly lower in patients older than 40 years, lower educational status, nonprivate insurance and with higher Charlson Comorbidity Scores. In addition, the use of systemic therapy was lower with female sex, African Americans/Hispanic, and lower socio-economic status. Understanding the barriers in the use of systemic therapy as well as appropriate utilization of systemic therapy can both optimize cancer care.

Chemotherapy use in stage III colon cancer: a National Cancer Database analysis.

Background: Although adjuvant chemotherapy in stage III colon cancer improves overall survival, prior studies have shown that it is underused. We analyzed different factors that may influence its use. Methods: This is a retrospective study of stage III colon cancer patients (n = 207,718) diagnosed between 2000 and 2011 in the National Cancer Data Base (NCDB). The NCDB contains ~70% of new cancer diagnosis from >1500 American College of Surgeons accredited cancer programs in the United States and Puerto Rico. The chi-squared test was used to determine any difference in characteristics of patients who did or did not receive chemotherapy. Results: A total of 35% of all stage III colon cancer patients, and 38% of stage III cases undergoing surgery, did not receive adjuvant chemotherapy. The use of chemotherapy had increased in recent years (64% in 2007–2011 versus 59% in 2000–2002; p < 0.0001). Its use was lower in whites (61%), females (60%), patients ⩾60 years (55%), patients with one or more comorbidities (55%), nonacademic centers (62%), those with medicare insurance (52%), lower education (61%) and income levels (59%, all p < 0.0001). The nonwhite and uninsured were more likely to be <60 years old. Conclusion: More than one-third did not receive adjuvant chemotherapy, although its use has increased in more recent years. Age was one of the most important determinants of chemotherapy use, which may explain higher rates in nonwhite and uninsured. In addition to patient characteristics, race, gender and socioeconomic factors influence chemotherapy use. These findings have important implications for healthcare reform.

Fondaparinux for Management of Heparin-induced Thrombocytopenia after Cardiovascular Intervention: A Systematic Review.

OBJECTIVESnThe efficacy and safety of fondaparinux, an emerging therapeutic option for heparin-induced thrombocytopenia (HIT), remain unclear in cardiac surgery patients with HIT.nnnMETHODSnUsing several search criteria, we reviewed all cases of fondaparinux use in patients who developed HIT after any cardiovascular intervention and were indexed in MEDLINE by August 2014. Based on pre-specified criteria, cases were divided into confirmed HIT, probable HIT and possible HIT. The outcome of fondaparinux use in each group was compared using Chi-square test.nnnRESULTSnOf 43 total cases, 22 had confirmed HIT and 21 had possible HIT. Valve replacement or repair (39%) and heart transplant or ventricular assist device placement (21%) were the most common preceding cardiovascular interventions. Creatinine clearance <30 ml was present in 27% and 52% of confirmed and possible HIT respectively. Overall the risk of new thrombosis and bleeding with fondaparinux were 4.6% and 7% respectively, without any differences in the two subgroups. The majority (86%) of cases improved clinically; of the remainder patients, similar percentage of cases with possible HIT and confirmed HIT died (24% vs. 5%; p= 0.102). None of the deaths were attributed to HIT or complications of bleeding.nnnCONCLUSIONnWithin the limitations of this study, the risk of thrombosis and bleeding with fondaparinux use in cardiac surgery patients with HIT are low and largely comparable to outcomes reported in literature with other agents.

Emerging Therapy Options in Heparin-Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a life and limb-threatening thrombotic complication of heparin, which is the result of platelet activation by anti-PF4/heparin antibodies. With lepirudin and danaparoid no longer available in the US, treatment options are limited to argatroban, fondaparinux (off-label use) and bivalirudin (for patients undergoing percutaneous coronary intervention). Both argatroban and bivalirudin are parenteral drugs and require close monitoring and hospitalization. Fondaparinux is contraindicated in patients with significant renal impairment and is associated with a small risk of HIT. Anticoagulants approved for thromboprophylaxis and management of thromboembolic conditions such as rivaroxaban, dabigatran, and apixaban have fixed oral dose, rapid onset of action and does not require monitoring. These novel agents do not interact with anti-PF4/heparin antibody and offer attractive therapy options for HIT. Their utility in HIT has been supported by a few clinical reports, however, larger studies are needed before they can be utilized in clinical practice. Therapeutic plasma exchange has been utilized with some success in patients with HIT, who need heparin reexposure for cardiac surgery but their safety and efficacy needs further exploration. 2-O, 3-O desulfated heparin, which lacks any anticoagulant effect, has been shown to reduce the development of HIT in murine models. Finally, novel targets based on the molecular pathogenesis of HIT are being studied for therapeutic drug development. We hope that the availability of novel therapies in the future will expand the options available for the management of HIT.

Bowel Perforation After Treatment with Sorafenib: A Case Report and Review of Literature

Sorafenib, one of the multitargeted tyrosine kinase inhibitors, is currently FDA approved for the treatment of advanced renal cell carcinoma (2005), unresectable hepatocellular carcinoma (2007), and differentiated thyroid carcinoma (2013) [1]. Prior studies have shown that bevacizumab therapy, a monoclonal antibody against vascular endothelial growth factor (VEGF), has significantly increased risk of gastrointestinal perforation with a relative risk of 2.14 (95 % CI 1.19–3.85; p=0.011) [2]. However, the association between gastrointestinal perforation and newer multitargeted tyrosine kinase inhibitors that inhibit other pathways in addition to VEGF is not well established [3]. We describe a case of bowel perforation in a patient on sorafenib and review the literature on similar cases.