Prajwal Dhakal

New Oral Anticoagulants for the Management of Heparin Induced Thrombocytopenia: A Focused Literature Review.

OBJECTIVE Drugs currently in use for the management of heparin-induced thrombocytopenia (HIT) have their limitations. Several new oral anticoagulants (NOACs) such as dabigatran, rivaroxaban and apixaban may offer attractive therapy options for HIT. Although the clinical data are sparse on this topic, we have summarized the available clinical data, discussed pertinent in-vitro studies and provided the rational and advantages of using NOACs in patients with suspected or confirmed HIT. We have also reviewed the safety and efficacy of these NOACs in patients with HIT based on published literature. METHODS We reviewed all suspected or confirmed HIT cases treated with NOACs and indexed in English language in MEDLINE and EMBASE by July 2015. The bibliography of each relevant article was searched for additional reports. In-vitro studies and other pertinent literature were briefly discussed. RESULTS A total of 36 HIT patients were treated with the following NOACs: rivaroxaban (50%), dabigatran (36%) and apixaban (14%). Sixty-one percent of patients received argatroban bolus before NOACs and 3% received rivaroxaban after a lack of response with three-day course of fondaparinux. Three percent (n=1) received rivaroxaban after the patient responded to intravenous immunoglobulin for 2 days, following a lack of response to fondaparinux and bilvalirudin. In another 3% (n=1), prophylactic dose of rivaroxaban was used for 21 days and then changed to dabigatran because of persistent thrombocytopenia. All cases responded with early signs of clinical improvement and increase in platelet counts. A follow-up after a median 47 days (range 4- 450) reported no bleeding or thrombotic complications. CONCLUSION In this review, all patients with HIT treated with NOACs responded without any bleeding or thrombotic complication. Although the argatroban bolus might have contributed to a response in some patients, response to NOAC alone in other patients and in-vitro studies provide a proof of principle that NOACs can be effective in the management of HIT. Additionally, properties such as rapid onset of action, oral administration, ease of use and a lack of need for monitoring make these drugs attractive options for HIT. However, given several limitations of prior reports, further confirmation of the results are desirable.

Reversal of Anticoagulation and Management of Bleeding in Patients on Anticoagulants.

Bleeding is the most common complication of all anticoagulants. Any bleeding patient on an anticoagulant should be risk-stratified based on hemodynamic instability, source of bleeding, and degree of blood loss. Although minor bleed may be managed with discontinuation of anticoagulant, major bleed may require transfusion of blood products and use of specific antidote. The residual effects of each anticoagulant may be monitored with distinct coagulation assay. Intravenous or oral vitamin K can reverse the effect of warfarin within 24 to 48 hours and is indicated for any bleeding, international normalized ratio of >10 or 4.5 to 10 in patients with other risk factors for bleeding. Fresh frozen plasma or prothrombin complex concentrate (PCC) may be necessary in major bleeding related to warfarin. Protamine sulfate reverses the effect of unfractionated heparin completely and of low-molecular-weight heparin (LMWH) partially. Idarucizumab has recently been approved in United States for dabigatran reversal, whereas andexanet alfa is expected to get approved in the near future for reversal of oral factor Xa inhibitors. The PCC may reverse the effect of rivaroxaban to some extent, but no data are available regarding reversal of apixaban and edoxaban. Aripazine has shown promising results to reverse the effects of LMWH, fondaparinux, and direct oral anticoagulants but is still in the developmental phase.

Mad Honey Poisoning: A Review

Mad honey, which is different from normal commercial honey, is contaminated with grayanotoxins and causes intoxication. It is used as an alternative therapy for hypertension, peptic ulcer disease and is also being used more commonly for its aphrodisiac effects. Grayanotoxins, found in rhododendron plant, act on sodium ion channels and place them in partially open state. They also act on muscarinic receptors. Cardiac manifestations of mad honey poisoning include hypotension and rhythm disorders such as bradycardia, nodal rhythm, atrial fibrillation, complete atrioventricular block or even complete heart block. Additionally, patients may develop dizziness, nausea and vomiting, weakness, sweating, blurred vision, diplopia and impaired consciousness. Diagnosis is made with history of honey intake and clinical presentation. Treatment is symptomatic. Patients presenting with severe hypotension and bradycardia may need prompt treatment with fluids, atropine or even temporary pacing if other measures fail. Although fatalities are rare, poisoning may be hard to recognize and arrhythmias may be life-threatening.

Spontaneous tumour lysis syndrome in small cell lung cancer: a rare phenomenon

Tumour lysis syndrome (TLS) is an oncological emergency. It is caused by cellular death occurring secondary to cancer therapy or spontaneously in rapidly dividing tumours. More common in haematological malignancies, it has also been reported in solid tumours. Out of 14 cases of small cell lung cancer (SCLC) with TLS, only three cases of spontaneous TLS have been reported in literature to date. Here we report a case of SCLC presenting as a spontaneous TLS.

Renal cancer in recipients of kidney transplant

The aim of our study is to determine characteristics and outcomes of kidney cancer in renal transplant recipients. MEDLINE® database was searched in June 2015 to identify cases of kidney cancer in renal transplant recipients. We include also a new case. Descriptive statistics were used for analysis. Forty-eight (48) recipients reported in 25 papers met the eligibility criteria. The median age was 47 years (range 9-66); 27% were females. Chronic glomerulonephritis, cystic kidney disease and hypertension were common indications for renal transplant. Among donors 24% were females and the median age was 52.5 years (17-73); 62% of kidney cancers were donor-derived. The median interval between transplant and cancer diagnosis was shorter for cancer of recipient versus donor origin (150 vs. 210 days). Clear cell carcinoma was diagnosed in 17%. 25% had metastasis at diagnosis. Kidney explantation or excision was done in 90% and 84% of cases with and without metastasis respectively. The median survival was 72 months. Actuarial 1-year and 5-year survival rates were 73.4% and 55.1% respectively. Among the recipients from 7 donors who subsequently developed malignancy, 57% were dead within a year. Kidney transplant recipients have a small risk of kidney cancer, which affects younger patients and occurs within a year of transplant, likely due to immunosuppression. Whether the use of older donors may increase the likelihood needs further investigation. The presence of metastasis, explantation or excision of affected kidney and development of cancer in donors predict outcomes. The results may guide patient education and informed decision-making.

Central nervous system complications after allogeneic hematopoietic stem cell transplantation

Allogenic hematopoietic stem cell transplant (alloSCT) is a potentially curative modality of treatment for patients with hematological malignancies. However, CNS complications following transplant pose a risk to survival of the patients. Early recognition and management of these complications are crucial to reduce morbidity and mortality of patients following transplant. Early CNS complications associated with alloSCT are infection, cerebrovascular events, chemotherapy and radiation-induced toxicities while late complications include post-transplant lymphoproliferative disorder, CNS relapse of underlying malignancy and viral and fungal infections. Development of graft-versus-host disease can further increase the risk of CNS complications and outcomes after alloSCT. Strategies aimed to reduce the risk of CNS complications and early management may ameliorate the morbidity and mortality in transplant recipients.

An Algorithmic Approach to Management of Venous Thromboembolism

Venous thromboembolism (VTE) is associated with significant morbidity and mortality. Factors such as the presence of transient risk factors for VTE, risk of bleeding, and location of deep vein thrombosis (DVT) determine the duration of anticoagulation. Extended anticoagulation is offered to patients with unprovoked pulmonary embolism (PE) or proximal DVT and a low risk of bleeding. Anticoagulation for 3 months is advised in patients with provoked DVT or PE, high risk of bleeding, and isolated distal or upper extremity DVT. In patients with unprovoked PE or proximal DVT and a low risk of bleeding, who want to stop anticoagulation after 3 months, further risk stratification is necessary. Clinical scoring system, and thrombophilia testing otherwise not routinely performed, may be considered to measure risk of annual recurrence in such cases. Short-term anticoagulation may be considered in subsegmental PE and superficial vein thrombosis, particularly if patients are at low risk of bleeding and have persistent risk factors for recurrent VTE. In cases of catheter-associated thrombosis, the catheter need not be removed routinely, and the patient may be anticoagulated for 3 months or longer if the catheter is maintained in patients with cancer. Extensive screening for occult cancer in cases of unprovoked VTE is not beneficial. New oral anticoagulants such as apixaban, rivaroxaban, or dabigatran may be preferred to vitamin K antagonists in patients without cancer or renal failure, more so after the development of reversal agents such as idarucizumab and andexanet alfa.

Chylothorax: A review of management options

Chylothorax is a rare condition caused by obstruction or injury to the thoracic duct leading to accumulation of chyle in the pleural cavity. A definitive guideline for management is lacking and most cases are managed with a staged care plan that moves from the least invasive options to more invasive interventions. First-line therapy consists of treatment of underlying conditions, pleural drainage to control symptoms, and dietary modifications. Surgical measures including pleurodesis and thoracic duct ligation are pursued if conservative measures are ineffective. In recent times, percutaneous image-guided interventions such as thoracic duct embolization and thoracic duct disruption are increasingly being used. These interventions have shown promising results and are used to manage patients with failed conservative therapy, high-output chylothorax, and those who cannot tolerate surgical procedures.