Optimization of warfarin dose by population-specific pharmacogenomic algorithm.

To optimize the warfarin dose, a population-specific pharmacogenomic algorithm was developed using multiple linear regression model with vitamin K intake and cytochrome P450 IIC polypeptide9 (CYP2C9(*)2 and (*)3), vitamin K epoxide reductase complex 1 (VKORC1(*)3, (*)4, D36Y and -1639 G>A) polymorphism profile of subjects who attained therapeutic international normalized ratio as predictors. New algorithm was validated by correlating with Wadelius, International Warfarin Pharmacogenetics Consortium and Gage algorithms; and with the therapeutic dose (r=0.64, P<0.0001). New algorithm was more accurate (Overall: 0.89 vs 0.51, warfarin resistant: 0.96 vs 0.77 and warfarin sensitive: 0.80 vs 0.24), more sensitive (0.87 vs 0.52) and specific (0.93 vs 0.50) compared with clinical data. It has significantly reduced the rate of overestimation (0.06 vs 0.50) and underestimation (0.13 vs 0.48). To conclude, this population-specific algorithm has greater clinical utility in optimizing the warfarin dose, thereby decreasing the adverse effects of suboptimal dose.

Thrombophilia - how far and how much to investigate?

Thrombohemorrhagic balance is maintained by complicated interactions between the coagulation and fibrinolytic system, platelets, and the vessel wall. Dr. Virchow provided approach for investigating and managing thrombotic disorders. He proposed stasis, vascular injury, and hypercoagulability as causes for thrombosis. In 1965, antithrombin deficiency was described. After two decades, protein C and protein S deficiencies, mutations of factor V Leiden, and factor II were described. If we distinguish patients at high risk and low risk of thrombosis, we can optimize therapeutic decisions. There is currently no evidence to say that laboratory abnormality should influence intensity of anticoagulation. In this article we reviewed the risk factors and need for thrombophilia screening in patients. Screening general population for thrombophilia is not justified or recommended at this time.

Ruptured large carotid artery aneurysm.

Carotid artery aneurysms are rare [1]. Bifurcation of the common carotid artery is most frequently reported site of true aneurysm in the extracranial carotid system. Blunt injury of the neck involves high cervical portion of the internal carotid artery. Large aneurysms of the carotid artery can distort the anatomy and one can anticipate the intubation difficulties during anesthesia induction. A man aged 25 years, weighing 35 Kilograms was admitted in emergency with a large swelling (bleeding) on the right side of neck, covered with a bandage. In a rural hospital, biopsy was attempted, wounds were packed with gauze as there was profuse bleeding and referred the patient to our hospital. Spiral CT angiogram showed a large aneurysm arising from the bifurcation of the right common carotid artery. He complained of dysphagia for the past 20 days. In the CT scan the internal carotid artery was found to be occluded without neurological deficit. During surgery the common carotid, external carotid arteries were dissected out, clamped, ligated and thrombi were evacuated. The unhealthy and inflamed tissues were debrided. The wound was closed with a drain. Postoperative recovery was uneventful without neurological deficits.

Neurofibromas of saphenous nerve mimicking thrombophlebitis.

Young man aged 25 years complained of persistent pain on the medial side of the lower part of the thigh for 2 months. A cord like structure was palpable with 3 small nodular swelling parallel to the course of the long saphenous vein. Initially he was treated as a case of thrombophlebitis of saphenous vein in a clinic near his home. When the pain persisted after receiving injection heparin therapy, he was referred to the vascular surgery clinic. Duplex scan reported as thrombophlebitis of a vein parallel to the great saphenous vein. We continued the injection heparin and suspected thrombophilia. There were no other known risk factors for thrombosis. The pain persisted, so we excised the cord like structure with nodular swellings and biopsy reported it as neurofibromatosis of the saphenous nerve. Postoperatively the pain subsided dramatically and in the follow up clinic he mentioned about the paresthesias in the distribution area of saphenous nerve. Diagnosis of the small tumors of the peripheral nerves is difficult at this site and they can be easily mistaken for thrombophlebitis. Unusual pain and nodularity of the swelling as in this case can help us to consider early biopsy or excision of the tumor.

Schwannoma of the cervical vagus nerve.

Nerve sheath tumors arising from the cervical vagus nerve are extremely rare and difficult to diagnose. We report a 14-year-old boy who presented with a several month history of an asymptomatic right cervical swelling. Ultrasound and fine needle aspiration cytology revealed a vascular lesion. He was meticulously evaluated with CT scan and digital subtraction angiography. Surgical excision of the lesion was carried out and histological examination revealed a schwannoma. Schwannoma is a relatively rare tumor and even rarer in children. The incidence of such tumors and the management of our patients are discussed.

Floating thrombus in the brachio-cephalic trunk.

Floating thrombus in a non-aneurysmal and non-atherosclerotic brachio-cephalic trunk is an extremely rare event with potentially catastrophic complications. There is a risk of both peripheral and cerebral embolization. We present a very rare case of floating thrombus in the brachio-cephalic trunk that presented with advanced ischaemia of the right upper limb. Confirmation of the diagnosis was done by CT angiogram. The upper limb symptoms were relieved by thrombectomy, supported by anticoagulation. For floating thrombus in the brachiocephalic trunk, the patient was started on aggressive anticoagulation therapy and there was significant resolution after two weeks and complete resolution after one month.