A 63-year-old Caucasian woman without medical history stayed for several weeks in Cameroun, without taking any antimalarial chemoprophylaxis. She developed severe gastrointestinal symptoms and, after three days, due to her suspicion of a malaria attack, she took at once four pills of Coartem (each containing 20 mg artemether and 120 mg lumefantrine). After that, the patient became unable to ingest any food or drug and a transfer to Europe was rapidly decided. She became seriously ill during the flight back. On arrival at the airport, she was found stuporous and hypotensive and was rapidly transferred to the intensive care unit (ICU) of the nearest hospital. The diagnosis of Plasmodium falciparum malaria was rapidly made on the blood smear and treatment was started with intravenous quinine and doxycycline (as artesunate was not available). Parasitemia was estimated less than 1%. Admission coagulation tests revealed activated partial thromboplastin time 37 sec, international normalized ratio 1.2, fibrinogen 299 mg/dL, D-dimers >8000 ng/mL (normal, <500), ADAMTS13 activity undetectable (reference range, 50–150%), von Willebrand factor (VWF) antigen 340% (reference range, 50–150%), and platelet count 21,000/mm³. Early complications included refractory hypotension and hypoxemia and neurological worsening. Intubation was required for mechanical ventilation; norepinephrine infusion was progressively increased to the maximal infusion rate of 46 μg/min. An acute left ventricular dysfunction could be demonstrated at echocardiography. Continuous venovenous hemofiltration was initiated for acute renal failure. Due to the evidence of multiple organ failure and despite relatively low parasitemia, exchange transfusion therapy was performed. Only one session of 87 minutes was performed. The patient's theoretical total blood volume was 4407 mL; on the whole, 1409 mL of red blood cells was removed and replaced by 1277 mL of packed red blood cells. Blood coagulation tests remained disturbed, with epistaxis and rectal bleeding. The nadir of platelet count (5,000/mm³) and plasma fibrinogen (66 mg/dL) was noted on day 4, but there was only a mild increase in activated partial thromboplastin time and prothrombin time. The activity of ADAMTS13 slightly increased to 32%; no inhibitor or ADAMTS13 autoantibodies were found. From day 2, blackish discoloration of both hands and feet was noted and by the following days a definite line of demarcation was observed between gangrenous and normal skin (). Ultrasound-Doppler examination confirmed the absence of distal perfusion. Plastic surgeon suggested postponing the extensive surgery. Further clinical course was characterized by repeated candidemia (days 4, 7, 9, 10, and 11) and bacteraemia (Pseudomonas aeruginosa on day 7 and Enterococcus faecalis on days 12, 13, and 18), despite appropriate antifungal and antimicrobial therapy. The abdomen computed tomography (CT) failed to reveal bowel ischemia, but diffuse thickening of the jejunal wall was found. Endoscopy on day 11 disclosed multiple duodenal ulcerations from ischemic origin (); colonoscopy performed on day 28 was also consistent with ischemic injury disseminated in the sigmoid colon (). Norepinephrine infusion had been definitely stopped on day 14. The patient regained consciousness progressively from day 22 and extubation was possible on day 32.\nThe decision to perform quadriamputation was discussed after recovery from the critical period, when she became able to give her consent. Surgery was performed two months after the first signs of peripheral gangrene. Renal function recovered and the patient was further transferred for rehabilitation.
A 50-year-old uneducated male of low socioeconomic status was scheduled for amputation of toes. To start with, he had complaint of fever associated with chills and rigors for 3 weeks. He consulted a local practitioner who prescribed some tablets about which patient could not give the details. He noticed blackening of toes of both the feet, which was slow and progressive over 1 week. As he was not responding to the treatment, he was rushed to our medical college. There was no history of trauma, significant drug ingestion particularly ergot, alcohol consumption or smoking. On physical examination, he was febrile, dehydrated, and had pallor; there was no icterus, cyanosis, edema, or significant lymphadenopathy. A pulse rate of 120/min, respiratory rate of 24/min, and blood pressure of 90/70 mmHg was recorded. All peripheral pulses were palpable. On systemic examination, mild hepatosplenomegaly was present and rest of the systemic examination was normal. On local examination, there was blackish discoloration of all toes, extending up to malleoli [Figures and ]. Intavenous line was secured. Ringer lactate was started and investigations were sent for. Reports were as follows [].\nPeripheral blood smear showed ring forms of P. falciparum with occasional gametocytes. Three consecutive blood cultures for bacteria were negative. Color Doppler study of the lower limbs revealed normal flow in both the femorals and the popliteal, with slightly reduced flow in tibial and dorsalis pedis artery with hypoechogenic shadow in its lumen.\nThe patient was given i.v. quinine, loading dose of 20 mg/kg followed by a maintenance dose of 10 mg/kg thrice a day for 2 days. Then, the patient was shifted to oral quinine (dose 10 mg/kg) thrice a day and oral paracetamol 500 mg thrice a day for 5 days. Two units of packed cell transfusion were also given. Fever subsided within 5 days of treatment. His peripheral smear for malarial parasite became negative after 7 days of quinine course. Line of demarcation did not progress any further. For management of gangrene, amputation was planned. All repeated blood investigations were within normal limits except prothrombin time 16.5 s, fibrinogen level 2.9 g/L (normal value 1.5-4 g/L), and D-dimer 1.7. The surgery was done under total i.v. anesthesia.