Hyperglycemic hyperosmolar state causing multiple thrombosis

Introduction: Diabetes mellitus is regarded as a pro-thrombotic state(1). Extreme hyperglycemia and dehydration in the hyperglycemic hyperosmolar state (HHS) add to the risk for thrombo-ischemic events(2,3). Lower limb ischemia and occlusion of the femoral arteries in HHS is a distinct association, but its development may be hard to recognize due to its infrequent occurrence in daily practice. Prompt recognition is important to prevent irreversible damage(3,4,5). Case Presentation: A 50-year old female was admitted to the intensive care unit (ICU) with epigastric pain for 1 day. She reported no other medical conditions except hypertension. Clinical examination showed a fully conscious female who was severely dehydrated. Clinical and laboratory parameters on admission are represented in Table 1. Based on a glucose level >30 mmol/L and an osmolarity >320 mOsm/L, HHS was diagnosed. Other investigations (septic work up, chest X ray, and ECG) were normal. The patient received a total of 9 liters of 0.9% saline with insulin/potassium over 6 hours. Dalteparin was given subcutaneously (5000 IU daily). On the second day of admission signs of acute ischemia were noticed in the left upper and left lower limbs. An ultrasound doppler and CT angiography confirmed the occlusion of the left subclavian, left femoral artery and aortic arch thrombosis (Figures 1A). Echocardiography showed a thrombus in the aortic arch. An emergency thrombectomy of the brachial and femoral arteries and a left arm fasciotomy took place and therapeutic unfractionated heparin infusion was started. A thrombophilia work up for antiphospholipid syndrome, heparin induced thrombocytopenia, complements 3 and 5, antinuclear antibody (ANCA), lupus screen, homocysteine, antithrombin, Factor V leiden, anticardiolipin, anti-B2 glycoprotein, protein S and C activity were normal. The patient and the family denied a personal or family history of thromboembolic events. On the fifth day post-admission, the patient developed septic shock with multi-organ failure (circulatory, respiratory, renal, and coagulation). The patient responded to ICU management. Parameters of her coagulation profile are given in Table 1. On the ninth day the patient developed dry gangrene in the left foot, which required a below the knee amputation. On the eleventh day the patient was extubated, neurological assessment was showing right-sided hemiparesis. The MRI was showing multiple microcerebral hemorrhages, an infarction in the left paramedian pons and a cerebellar infarction (Figures 1B). On the fourteenth day the patient developed abdominal distension. The CT showed partial mesenteric vein thrombosis despite the patient being on therapeutic heparin (Figure 2). On the seventeenth day the patient had a tracheostomy and was discharged from the ICU for rehabilitation on a therapeutic dose of dalteparin. Conclusion: Current guidelines provide for thromboprophylaxis in HHS, i.e., heparin during admission. This covers the risk for deep venous thrombosis (DVT), but might be insufficient in case of an imminent arterial thrombosis, especially in cases of long existing diabetes. Alternative therapy targeting crucial factors in the coagulation pathway leading to an arterial thrombus should be searched. The development of an algorithm for thromboprophylaxis in a hyperglycemic crisis needs our attention to improve the outcome of this high-risk condition.